Toxoplazmoza – Patofizjologia i mechanizm

Toxoplazmoza
Patofizjologia i mechanizm

Toksoplazmoza, wywoływana przez wewnątrzkomórkowego pierwotniaka Toxoplasma gondii, jest powszechną chorobą pasożytniczą o globalnym zasięgu, zainfekującą około jednej trzeciej populacji światowej. Pasożyt posiada złożony cykl życiowy, w którym koty stanowią żywiciela ostatecznego, a u ludzi występuje w formach tachyzoitów, bradyzoitów i oocyst. Zarażenie następuje głównie przez spożycie niedogotowanego mięsa z cystami, kontakt z oocystami lub zakażenie przezłożyskowe. Tachyzoity aktywnie penetrują komórki gospodarza, namnażając się w wakuolach pasożytniczych, co prowadzi do martwicy tkanek i rozprzestrzeniania się pasożyta, zwłaszcza w mięśniach, mózgu i oczach. U osób z upośledzoną odpornością, w tym pacjentów z AIDS (CD4 <200/μL), toksoplazmoza może prowadzić do ciężkich powikłań, takich jak zapalenie mózgu, zapalenie płuc czy retinochoroiditis. Wrodzona toksoplazmoza wiąże się z ryzykiem zakażenia płodu wynoszącym 25% w I trymestrze i 65% w III trymestrze, z poważnymi konsekwencjami neurologicznymi i oftalmologicznymi.

Wprowadzenie do toksoplazmozy

Toksoplazmoza jest chorobą pasożytniczą wywoływaną przez Toxoplasma gondii, wewnątrzkomórkowego pierwotniaka z grupy apikompleksów. Pasożyt ten występuje na całym świecie i może infekować praktycznie wszystkie zwierzęta stałocieplne, w tym ludzi¹². Według szacunków nawet jedna trzecia światowej populacji (ponad 2 miliardy ludzi) może być zarażona tym pasożytem³⁴. T. gondii ma złożony cykl życiowy, w którym kot (oraz inne kotowate) jest jedynym żywicielem ostatecznym, gdzie pasożyt może się rozmnażać płciowo⁵⁶.

Istnieją trzy główne genotypy T. gondii (typ I, typ II i typ III), które różnią się patogennością i częstością występowania u ludzi. W Europie i Stanach Zjednoczonych, genotyp II jest odpowiedzialny za większość przypadków wrodzonej toksoplazmozy⁷⁸. Chociaż T. gondii zakaża znaczną część światowej populacji, rzadko wywołuje klinicznie istotną chorobę. Jednak niektóre osoby są narażone na ciężką lub zagrażającą życiu toksoplazmozę – należą do nich płody, noworodki oraz pacjenci z upośledzoną odpornością⁹.

Cykl życiowy i drogi zakażenia

Toxoplasma gondii występuje w trzech formach morfologicznych: tachyzoity (forma szybko namnażająca się), bradyzoity (forma wolno namnażająca się w cystach tkankowych) oraz oocysty (forma powstająca wyłącznie w żywicielu ostatecznym)¹⁰¹¹.

Zarażenie T. gondii u ludzi może nastąpić na trzy główne sposoby:¹²

Spożycie niedogotowanego mięsa zawierającego cysty tkankowe z bradyzoitami
Spożycie żywności lub wody zanieczyszczonej oocystami
Zakażenie przezłożyskowe płodu tachyzoitami podczas pierwotnej infekcji matki

Po spożyciu przez kota zainfekowanej ofiary lub surowego mięsa, pasożyt jest uwalniany z cyst do przewodu pokarmowego kota, gdzie namnaża się i produkuje oocysty. Kot może wydalać miliony oocyst dziennie przez 1-3 tygodnie¹³. Oocysty są bardzo odporne i mogą pozostać zakaźne przez ponad rok w wilgotnym i ciepłym środowisku¹⁴.

U człowieka, po spożyciu oocyst lub cyst tkankowych, bradyzoity lub sporozoity penetrują komórki nabłonkowe jelita i namnażają się w jelicie. T. gondii może rozprzestrzeniać się zarówno lokalnie do krezkowych węzłów chłonnych, jak i do odległych narządów przez inwazję układu limfatycznego i krwi¹⁵¹⁶.

Przenikanie przez bariery tkankowe

Kluczowym krokiem w ustanowieniu infekcji i późniejszym przeżyciu i namnażaniu pasożyta jest jego przyłączenie i transmiejscowa migracja przez barierę nabłonkową jelita¹⁷. T. gondii wykształcił wysoce wyspecjalizowane strategie szybkiego przekraczania jednowarstwowej bariery nabłonkowej jelita¹⁸.

Transmiejscowa migracja pasożyta drogą parakomórkową między sąsiadującymi komórkami umożliwia rozprzestrzenianie się pasożyta do wtórnych miejsc infekcji, gdzie ustanawiana jest przewlekła infekcja tkanki mięśniowej i mózgowej¹⁹. Zidentyfikowano trzy możliwe drogi przejścia tachyzoitów przez śródbłonek siatkówki:²⁰

Transport w leukocytach (mechanizm „konia trojańskiego”)
Swobodny pasożyt przez drogę parakomórkową
Zakażenie komórek śródbłonka

Badania wykazały, że monocyty są odpowiedzialne za dotarcie T. gondii do mózgu. Ponadto, niedawne badania pokazały, że chociaż wszystkie komórki dendrytyczne (DC) migrują przez śródbłonek siatkówki, te zakażone przez T. gondii wykazują hipermobilność, a zatem lepszą zdolność do migracji w porównaniu do niezakażonych²¹.

Mechanizm umożliwiający tachyzoitom przemieszczanie się drogą parakomórkową prawdopodobnie obejmuje interakcję z molekułami adhezji komórkowej i międzykomórkowymi połączeniami ścisłymi. Tachyzoity mogą pozostać zakaźne i przetrwać poza komórkami gospodarza przez długie okresy, zachowując zdolność przylegania do śródbłonka siatkówki²².

Mechanizmy inwazji komórki gospodarza

Toxoplasma gondii ma zdolność do aktywnego wnikania do komórek gospodarza, co prowadzi do utworzenia wakuoli pasożytniczej pochodzącej z błony komórkowej, która jest całkowicie odmienna od normalnego przedziału fagocytarnego czy endocytarnego²³.

Inwazja komórki

Po przyłączeniu apikalnym, pasożyt szybko wnika do komórki gospodarza w procesie, który jest znacznie szybszy niż fagocytoza. Wakuola tworzy się głównie przez wpuklenie błony komórkowej gospodarza, która jest naciągana na pasożyta poprzez skoordynowane działanie cytoszkieletu aktynowo-miozynowego pasożyta²⁴.

T. gondii zawiera organelle zwane roptriami i mikronemiami. Zawierają one białka służące do inwazji i efektory do manipulowania odpowiedzią immunologiczną gospodarza. Do wstrzyknięcia ich do komórek gospodarza, T. gondii wykorzystuje kompleks apikalny zlokalizowany w czubku komórki, aby przebić błonę gospodarza i uwolnić zawartość tych organelli²⁵.

Po wniknięciu do komórki gospodarza, tachyzoity namnażają się wewnątrz wyspecjalizowanych wakuoli (zwanych wakuolami pasożytniczymi) utworzonych z błony komórki gospodarza podczas inwazji. Tachyzoity mnożą się wewnątrz tej wakuoli, aż komórka gospodarza umrze i pęknie, uwalniając i rozprzestrzeniając tachyzoity przez krwiobieg do wszystkich narządów i tkanek ciała, w tym mózgu²⁶.

Białka ROP i manipulacja odpowiedzią immunologiczną

Podczas wnikania do komórki, pasożyt uwalnia białka ROP z roptrii. Białka te przemieszczają się do jądra i powierzchni błony wakuoli pasożytniczej, gdzie mogą aktywować szlaki STAT, modulując ekspresję cytokin na poziomie transkrypcyjnym, wiązać i dezaktywować białka IRG niszczące błonę wakuoli pasożytniczej, a także wywoływać inne możliwe efekty²⁷.

Dodatkowo, niektóre szczepy T. gondii mogą wydzielać białko znane jako GRA15, aktywujące szlak NF-κB, który zwiększa regulację prozapalnej cytokiny IL-12 we wczesnej odpowiedzi immunologicznej, potencjalnie prowadząc do fazy latentnej pasożyta²⁸. Zdolność pasożyta do wydzielania tych białek zależy od jego genotypu i wpływa na jego wirulencję²⁹.

Patogeneza toksoplazmozy

Komórki gospodarza są niszczone przez aktywne namnażanie się T. gondii. Może to prowadzić do ogniskowej martwicy³⁰. Toxoplasma gondii nie wytwarza toksyny; martwica jest spowodowana wewnątrzkomórkowym namnażaniem się tachyzoitów³¹³².

Uszkodzenia tkanek i odpowiedź immunologiczna

Tachyzoity namnażają się, tworząc ogniska martwicze otoczone reakcją komórkową. Po rozwinięciu się normalnej odpowiedzi immunologicznej, tachyzoity znikają z tkanek. U osób z niedoborem odporności ostra infekcja postępuje, prowadząc do potencjalnie śmiertelnych konsekwencji, takich jak zapalenie płuc, zapalenie mięśnia sercowego i martwicze zapalenie mózgu³³³⁴.

Cysty tkankowe tworzą się już 7 dni po zakażeniu i pozostają przez całe życie gospodarza. Cysty tkankowe mają do 60 μm średnicy, każda zawierająca do 60 000 organizmów. Wywołują one niewielką lub żadną reakcję zapalną, ale mogą powodować nawracającą chorobę u pacjentów z niedoborem odporności lub retinochoroiditis u starszych dzieci z wrodzoną infekcją³⁵.

Zmiany w subpopulacjach limfocytów T są głębokie i długotrwałe podczas ostrej nabytej infekcji T. gondii. Zostały one skorelowane z zespołami chorobowymi, ale nie z wynikiem choroby³⁶.

Chroniczna infekcja i cysty tkankowe

Przewlekła infekcja występuje 2 do 3 tygodni po zakażeniu, gdy rozpoczyna się produkcja cytokin i przeciwciał przeciwko wielu białkom T. gondii. Pozakomórkowe tachyzoity są usuwane z tkanek gospodarza, a wewnątrzkomórkowe pasożyty różnicują się w utajone formy bradyzoitów otoczone wakuolą pasożytniczą zamkniętą w ścianie cysty³⁷.

Po początkowym okresie infekcji charakteryzującym się proliferacją tachyzoitów w całym organizmie, ciśnienie ze strony układu odpornościowego gospodarza powoduje, że tachyzoity T. gondii przekształcają się w bradyzoity, półuśpioną, wolno dzielącą się komórkową fazę pasożyta³⁸.

Bradyzoity mogą być reaktywowane i przekształcać się w szybko dzielące się tachyzoity przy osłabieniu układu odpornościowego gospodarza³⁹. Reaktywacja prawdopodobnie wynika z pęknięcia cysty i ponownego namnażania się bradyzoitów w tachyzoity⁴⁰.

Toksoplazmoza w poszczególnych narządach

Neurotoksoplazmoza

U człowieka pasożyty tworzą cysty tkankowe, najczęściej w mięśniach szkieletowych, mięśniu sercowym, mózgu i oczach; cysty te mogą pozostać przez całe życie gospodarza⁴¹⁴². Toxoplasma gondii wykazuje wyraźny tropizm do mózgu i oczu⁴³.

Najważniejszą manifestacją toksoplazmozy u płodu jest zapalenie mózgu i rdzenia kręgowego, które może mieć poważne konsekwencje⁴⁴. Większość przypadków toksoplazmozy u pacjentów z niedoborem odporności jest konsekwencją latentnej infekcji i reaktywacji. U pacjentów z AIDS, cysty tkankowe T. gondii mogą reaktywować się przy liczbie CD4 poniżej 200 komórek/μL; przy liczbie poniżej 100 komórek/μL, choroba kliniczna staje się bardziej prawdopodobna⁴⁵.

Toxoplasma gondii jest najczęstszą zakaźną przyczyną ogniskowych zmian mózgowych u pacjentów z HIV. Szczególnie w zaawansowanym stadium HIV może powodować znaczącą chorobowość i śmiertelność⁴⁶.

Badania wykazały, że specyficzne komórki odpornościowe, zwane komórkami CD8+ T lub komórkami T-zabójcami, odgrywają kluczową rolę w kontrolowaniu pasożyta w mózgu. Zespół badawczy wykazał, że pasożyt jest kontrolowany w mózgu przez rezydentne komórki CD8+ T, w przeciwieństwie do innych limfocytów, które patrolują narządy i tkanki limfoidalne⁴⁷.

Toksoplazmoza oczna

Zakażenie oczu Toxoplasma, ważna przyczyna retinochoroiditis w Stanach Zjednoczonych, może być wynikiem infekcji wrodzonej lub infekcji po urodzeniu⁴⁸. Głównym punktem wejścia pasożyta do tylnego odcinka oka jest krążenie siatkówkowe. Rzadko może uzyskać dostęp przez krążenie naczyniówkowe, jak widać w przypadkach punktowej zewnętrznej retinopatii toksoplazmozowej, gdzie RPE i zewnętrzna siatkówka są selektywnie dotknięte⁴⁹.

Aktywne zapalenie ma tendencję do ustępowania w ciągu kilku miesięcy, tworząc blizny, a reaktywacja obok starych blizn jest często obserwowana w toksoplazmozie ocznej⁵⁰. Niedawny model mysi zakażenia T. gondii ujawnił, że ferroptoza może być zaangażowana w zakażenie fotoreceptorów podczas ocznej toksoplazmozy⁵¹.

Celem leczenia jest zatrzymanie namnażania się pasożyta podczas aktywnej fazy i zminimalizowanie uszkodzenia tkanek wewnątrzgałkowych. Klasyczny schemat chemoterapeutyczny dla retinochoroidzy toksoplazmowej składa się z pirymetaminy i sulfadiazyny, plus kortykosteroidów⁵².

Toksoplazmoza wrodzona

Wrodzona toksoplazmoza wynika z ostrej pierwotnej infekcji nabytej przez matkę podczas ciąży⁵³. Ryzyko zakażenia płodu wynosi 25% w I trymestrze (ciężkość jest wysoka) i 65% w III trymestrze⁵⁴.

Tachyzoity mogą być przenoszone do płodu, powodując martwicę w wielu narządach⁵⁵. Ostra infekcja z tachyzoitami w krwiobiegu podczas ciąży stwarza możliwość zakażenia przezłożyskowego. Tachyzoity kolonizują łożysko i mogą przekroczyć barierę, aby dotrzeć do płodu w 30% przypadków, prowadząc do choroby⁵⁶.

Częstość przenoszenia tachyzoitów do płodu jest związana z wiekiem ciążowym, z niskimi wskaźnikami przenoszenia w pierwszym trymestrze (10-15%) i najwyższymi wskaźnikami przenoszenia w trzecim trymestrze (60-90%). Jednak choroba jest bardziej poważna, jeśli infekcja jest nabyta we wczesnej ciąży⁵⁷.

Zakażenie przezłożyskowe (przez tachyzoity) może prowadzić do:⁵⁸

Subklinicznej infekcji (60%)
Zapalenia mózgu
Wodogłowia
Małogłowia
Retinochoroiditis
Poronienia (10%)

Toksoplazmoza u osób z niedoborem odporności

Toksoplazmoza u pacjentów leczonych lekami immunosupresyjnymi może wynikać z nowo nabytej lub reaktywowanej latentnej infekcji⁵⁹. W latach 80. toksoplazmoza stała się jedną z chorób oportunistycznych związanych z pacjentami z niedoborem odporności, takimi jak pacjenci z AIDS, pacjenci po przeszczepach i pacjenci z nowotworami leczeni lekami immunosupresyjnymi⁶⁰.

Oportunistyczna toksoplazmoza u pacjentów z AIDS zwykle reprezentuje reaktywację przewlekłej infekcji. Dominującą zmianą w toksoplazmozowym zapaleniu mózgu u tych pacjentów jest martwica, która często prowadzi do wielu ropni, niektórych wielkości piłki tenisowej⁶¹.

U osób poddawanych immunosupresyjnej terapii lub cierpiących na chorobę immunosupresyjną, taką jak zespół nabytego niedoboru odporności (AIDS), toksoplazmoza może powodować powiększenie węzłów chłonnych, zaburzenia oczu i ośrodkowego układu nerwowego, choroby układu oddechowego i choroby serca⁶².

Mechanizmy molekularne i manipulacja gospodarzem

Mechanizmy unikania odpowiedzi immunologicznej

Pasożyt wpływa również na mechanizm anty-apoptotyczny, pozwalając zakażonym komórkom gospodarza na przetrwanie i replikację. Jedną z metod oporności na apoptozę jest zakłócanie pro-apoptotycznych białek efektorowych, takich jak BAX i BAK. Aby zakłócić te białka, T. gondii powoduje zmiany konformacyjne białek, które zapobiegają transportowi białek do różnych przedziałów komórkowych, gdzie inicjują one zdarzenia apoptotyczne⁶³.

T. gondii ma również zdolność do inicjowania autofagii komórek gospodarza. Prowadzi to do zmniejszenia liczby zdrowych, niezakażonych komórek, a w konsekwencji do mniejszej liczby komórek gospodarza atakujących zakażone komórki⁶⁴.

Co ciekawe, aby oprzeć się odpowiedzi immunologicznej, T. gondii z powodzeniem wyewoluował strategie unikania układu odpornościowego gospodarza i migracji do miejsc uprzywilejowanych immunologicznie, takich jak ośrodkowy układ nerwowy. T. gondii zapobiega wejściu układu odpornościowego gospodarza poprzez wiele mechanizmów, w tym regulację transkrypcyjną i zakłócanie sygnalizacji komórkowej, co prowadzi do wydzielania cytokin zapalnych, modulacji metaloproteinaz macierzy (MMP), produkcji molekuł mikrobójczych i apoptozy⁶⁵.

Wpływ na neurotransmitery i zachowanie

Pasożyt zmienia zachowanie swoich żywicieli pośrednich, zmniejszając ich wrodzony strach przed zapachem kota, a tym samym prawdopodobnie zwiększając prawdopodobieństwo, że żywiciel ostateczny pożre zainfekowanego żywiciela⁶⁶. Model gryzoni T. gondii jest jednym z najbardziej badanych modeli pasożytniczej manipulacji behawioralnej⁶⁷.

Mechanizm odpowiedzialny za zmiany behawioralne jest częściowo przypisywany zwiększonemu metabolizmowi dopaminy, który może być neutralizowany przez leki o działaniu antagonistycznym wobec dopaminy. T. gondii ma dwa geny, które kodują dwufunkcyjną hydroksylazę fenyloalaniny i tyrozyny, dwa ważne i ograniczające szybkość etapy biosyntezy dopaminy⁶⁸.

Przez ponad 40 lat wiadomo, że neuroprzekaźniki są zaangażowane w patogenezę schizofrenii. Stibbs doszedł do wniosku, że T. gondii powoduje nieprawidłowości w metabolizmie katecholamin i że mogą one być czynnikami przyczyniającymi się do zmian psychologicznych i motorycznych obserwowanych u eksperymentalnie zakażonych gryzoni⁶⁹.

W 2009 roku dr Glenn McConkey i jego koledzy z Uniwersytetu w Leeds w Wielkiej Brytanii wykazali, że T. gondii ma geny kodujące dwa krytyczne enzymy potrzebne do wytworzenia dopaminy. To odkrycie sugeruje możliwość, że nadmiar dopaminy, który ma występować u osób ze schizofrenią, może być wprowadzany przez T. gondii, a nie wytwarzany przez dotknięte osoby⁷⁰.

Oprócz wpływania na dopaminę, jest teraz jasne, że T. gondii może również wpływać na układy neuroprzekaźników GABA i glutaminianu⁷¹. Badanie wykazało, że 3 szczepy T. gondii (typy I, II i III) wywierały znacząco różne wpływy na dopaminę, glutaminian i serotoninę, a także na 2 neuropeptydy⁷².

Neuropsychologiczne efekty toksoplazmozy

Do niedawna, przewlekła latentna toksoplazmoza była uważana za łagodny stan, jednak zaproponowano i potwierdzono głównie badaniami eksperymentalnymi, że taki stan może mieć niszczący wpływ na układ neuropsychologiczny poprzez różne wprowadzone mechanizmy⁷³.

Po wejściu do ludzkiego ciała w formie cyst tkankowych, przejściu poza żołądek, pasożyt uwalnia się w jelitach, przekracza nabłonek jelitowy, kontynuując namnażanie się. Gdy znajdzie się w krwiobiegu, w swojej wewnątrzkomórkowej lokalizacji, może być przenoszony po całym ciele. Toxoplasma ma szczególny tropizm do tkanek mięśniowych i mózgowych, gdzie może pozostawać w formie cystycznej przez całe życie człowieka⁷⁴.

Toksoplazmoza a schizofrenia

Istnieje kilka wyjaśnień dla związku między toksoplazmozą a schizofrenią. Toxoplasma spp. jest pasożytem neurotropowym, mającym szczególne powinowactwo do komórek glejowych. Cysty składające się z bradyzoitów można znaleźć w całym mózgu. Cysty te mogą prowadzić do zmian psychologicznych poprzez ich anatomiczną lokalizację⁷⁵.

Toxoplasma spp. niekorzystnie wpływa na neurony dopaminergiczne poprzez zwiększenie poziomu substancji prozapalnych, takich jak cytokiny. Nawet w późniejszych stadiach choroby przewlekłej, Toxoplasma spp. produkuje hydroksylazę tyrozyny, a enzym ten powoduje ograniczenie syntezy dopaminy, a niedobór dopaminy może być związany z chorobą Parkinsona⁷⁶.

Toksoplazmoza a epilepsja

Istnieją badania kliniczno-kontrolne wykazujące wyższą częstość występowania seropozytywności dla toksoplazmozy u pacjentów z kryptogenną padaczką⁷⁷. Chociaż istnieją prawdopodobne mechanizmy i metaanalizy wspomniane powyżej, istnieje potrzeba większej liczby badań klinicznych, aby uzyskać silne dane dotyczące związku między toksoplazmozą a padaczką⁷⁸.

Nowe kierunki badań i perspektywy terapeutyczne

Głębsze zrozumienie mechanizmów nadzoru immunologicznego nad pasożytem toksoplazmozy w mózgu może sugerować nowe strategie terapeutyczne mające na celu stymulowanie naturalnej odporności na pasożyta w celu lepszego powstrzymania lub nawet wyeliminowania go⁷⁹.

Naukowcy z uniwersytetów w Genewie i Zurychu oraz PSI zidentyfikowali strukturę i funkcje RON13, enzymu pasożyta toksoplazmozy, który jest niezbędny dla mechanizmu zakaźnego u ludzi. Zrozumienie, w jaki sposób pasożyt zdołuje wniknąć do komórek gospodarza, oferuje nowe możliwości opracowania bardziej skutecznych strategii zapobiegania i kontroli niż te obecnie dostępne⁸⁰.

Badania pokazują, że jeśli zaprojektujemy nowe leki, które celują w ten szlak odpowiedzi na stres, leki te mogą być skuteczne zarówno przeciwko ostrej, jak i przewlekłej infekcji Toxoplasma⁸¹.

Toxoplasma gondii manipuluje odpowiedzią immunologiczną poprzez hamowanie lub stymulowanie cytokin, co sugeruje potencjał do kontrolowania i utrzymywania zrównoważonego układu odpornościowego. Dodatkowo, T. gondii ma również unikalną cechę bycia tzw. bakterią trojańskiego konia, która może być wykorzystana jako system dostarczania leków do leczenia regionów, które były odporne na poprzednie terapie dostarczania leków⁸².

Dostawa leków za pośrednictwem T. gondii wykorzystuje komórki odpornościowe, które są zaangażowane w różne choroby, a to podejście może być zastosowane do różnych chorób, dla których dotychczasowa dostawa leków była trudna, w tym nowotworów⁸³.

Diagnostyka toksoplazmozy

Toksoplazmoza jest diagnozowana na podstawie badań serologicznych, które są rutynową metodą diagnostyczną⁸⁴. Wykrywanie materiału genetycznego pasożyta za pomocą PCR jest szczególnie przydatne w wykrywaniu zakażeń wrodzonych in utero i zapalenia mózgu toksoplazmozowego u osób z HIV⁸⁵.

Wykrywanie przeciwciał specyficznych dla Toxoplasma jest główną metodą diagnostyczną w celu określenia zakażenia Toxoplasma⁸⁶. Awidność przeciwciał IgG przeciwko T. gondii jest użytecznym markerem do różnicowania między niedawną a odległą infekcją⁸⁷.

Toksoplazmozę diagnozuje się za pomocą metod biologicznych, serologicznych lub histologicznych; lub jakiejś kombinacji tych metod⁸⁸.

Kolejne rozdziały

Zapraszamy do dalszego czytania naszego leksykonu.

Wybierz kolejny rozdział z menu poniżej, aby otworzyć nową podstronę kompedium wiedzy i uzyskać szczegółowe informację o leku, substancji lub chorobie.

Materiały źródłowe

#1 Toxoplasmosis – Wikipedia
https://en.wikipedia.org/wiki/Toxoplasmosis
Toxoplasmosis is a parasitic disease caused by Toxoplasma gondii, an apicomplexan. Infections with toxoplasmosis are associated with a variety of neuropsychiatric and behavioral conditions. The parasite’s survival is dependent on a balance between host survival and parasite proliferation. T. gondii achieves this balance by manipulating the host’s immune response, reducing the host’s immune response, and enhancing the parasite’s reproductive advantage. Once it infects a normal host cell, it resists damage caused by the host’s immune system, and changes the host’s immune processes. As it forces its way into the host cell, the parasite forms a parasitophorous vacuole (PV) membrane from the membrane of the host cell. The PV encapsulates the parasite, and is both resistant to the activity of the endolysosomal system, and can take control of the host’s mitochondria and endoplasmic reticulum. When first invading the cell, the parasite releases ROP proteins from the bulb of the rhoptry organelle. These proteins translocate to the nucleus and the surface of the PV membrane where they can activate STAT pathways to modulate the expression of cytokines at the transcriptional level, bind and inactivate PV membrane destroying IRG proteins, among other possible effects. Additionally, certain strains of T. gondii can secrete a protein known as GRA15, activating the NF-B pathway, which upregulates the pro-inflammatory cytokine IL-12 in the early immune response, possibly leading to the parasite’s latent phase. The parasite’s ability to secrete these proteins depends on its genotype and affects its virulence. The parasite also influences an anti-apoptotic mechanism, allowing the infected host cells to persist and replicate. One method of apoptosis resistance is by disrupting pro-apoptosis effector proteins, such as BAX and BAK. To disrupt these proteins, T. gondii causes conformational changes to the proteins, which prevent the proteins from being transported to various cellular compartments where they initiate apoptosis events. T. gondii also has the ability to initiate autophagy of the host’s cells. This leads to a decrease in healthy, uninfected cells, and consequently fewer host cells to attack the infected cells. Research by Wang et al finds that infected cells lead to higher levels of autophagosomes in normal and infected cells. Their research reveals that T. gondii causes host cell autophagy using a calcium-dependent pathway. Another study suggests that the parasite can directly affect calcium being released from calcium stores, which are important for the signalling processes of cells. The mechanisms above allow T. gondii to persist in a host. Some limiting factors for the toxoplasma is that its influence on the host cells is stronger in a weak immune system and is quantity-dependent, so a large number of T. gondii per host cell cause a more severe effect. The effect on the host also depends on the strength of the host immune system. Immunocompetent individuals do not normally show severe symptoms or any at all, while fatality or severe complications can result in immunocompromised individuals. T. gondii has been shown to produce a protein called GRA28, released by the MYR1 secretory pathway, which interferes with gene expression in infected cells and results in cells that behave like dendritic cells, becoming highly mobile in the body. Since the parasite can change the host’s immune response, it may also have an effect, positive or negative, on the immune response to other pathogenic threats. This includes, but is not limited to, the responses to infections by Helicobacter felis, Leishmania major, or other parasites, such as Nippostrongylus brasiliensis.
#2 Toxoplasmosis – Infectious Diseases – Merck Manual Professional Edition
https://www.merckmanuals.com/professional/infectious-diseases/extraintestinal-protozoa/toxoplasmosis
T. gondii is ubiquitous in birds and mammals. This obligate intracellular parasite invades and multiplies asexually as tachyzoites within the cytoplasm of any nucleated cell. When host immunity develops, multiplication of tachyzoites ceases and tissue cysts form; cysts persist in a dormant state for years, especially in brain, eyes, and muscle. The dormant Toxoplasma forms within the cysts are called bradyzoites. […] After ingestion of oocysts or tissue cysts, tachyzoites are released and spread throughout the body. This acute infection is followed by the development of protective immune responses and the formation of tissue cysts in many organs. The cysts can reactivate causing disease, primarily in immunocompromised patients. Toxoplasmosis reactivates in 30 to 40% of AIDS patients who are not taking antibiotic prophylaxis, but the widespread use of trimethoprim/sulfamethoxazole for Pneumocystis prophylaxis has dramatically reduced the incidence. […] In the human host, parasites form tissue cysts, most commonly in skeletal muscle, myocardium, the brain, and the eyes; these cysts may remain throughout the life of the host and can reactivate if the host becomes immunocompromised.
#3 Toxoplasmosis: Background, Etiology and Pathophysiology, Epidemiology
https://emedicine.medscape.com/article/229969-overview
Toxoplasmosis is caused by infection with the protozoan Toxoplasma gondii, an obligate intracellular parasite. The infection produces a wide range of clinical syndromes in humans, land and sea mammals, and various bird species. T gondii has been recovered from locations throughout the world, except Antarctica. […] There are 3 major genotypes (type I, type II, and type III) of T gondii. These genotypes differ in their pathogenicity and prevalence in people. In Europe and the United States, type II genotype is responsible for most cases of congenital toxoplasmosis. […] T gondii infects a large proportion of the world’s population (perhaps one third) but uncommonly causes clinically significant disease. However, certain individuals are at high risk for severe or life-threatening toxoplasmosis. Individuals at risk for toxoplasmosis include fetuses, newborns, and immunologically impaired patients.
#4 Systems analysis points to links between Toxoplasma infection and common brain diseases – UChicago Medicine
https://www.uchicagomedicine.org/forefront/biological-sciences-articles/systems-analysis-points-to-links-between-toxoplasma-infection-and-common-brain-diseases
More than 2 billion people nearly one out of every three humans on earth, including about 60 million people in the United States have a lifelong infection with the brain-dwelling parasite Toxoplasma gondii. […] „We wanted to understand how this parasite, which lives in the brain, might contribute to and shed light on pathogenesis of other brain diseases,” said Rima McLeod, MD, professor of ophthalmology visual science and pediatrics and medical director of the Toxoplasmosis Center at the University of Chicago. […] „Our results provide insights into mechanisms whereby this parasite could cause these associated diseases under some circumstances,” the authors wrote. „This work provides a systems roadmap to design medicines and vaccines to repair and prevent neuropathological effects of T. gondii on the human brain.”
#5 Toxoplasmosis pathophysiology – wikidoc
https://www.wikidoc.org/index.php/Toxoplasmosis_pathophysiology
Toxoplasma gondii is a protozoan parasite that infects most species of warm blooded animals, including humans, causing the disease toxoplasmosis. Members of the cat family (Felidae) are the only known definitive hosts for the sexual stages of T. gondii and thus are the main reservoirs of infection. Cats become infected with T. gondii by carnivorism. After tissue cysts or oocysts are ingested by the cat, viable organisms are released and invade epithelial cells of the small intestine where they undergo an asexual followed by a sexual cycle and then form oocysts, which are excreted. The unsporulated oocyst takes 1 to 5 days after excretion to sporulate (become infective). Although cats shed oocysts for only 1 to 2 weeks, large numbers may be shed. Oocysts can survive in the environment for several months and are remarkably resistant to disinfectants, freezing, and drying, but are killed by heating to 70C for 10 minutes.
#6 Toxoplasmosis in Cats | Cornell University College of Veterinary Medicine
https://www.vet.cornell.edu/departments-centers-and-institutes/cornell-feline-health-center/health-information/feline-health-topics/toxoplasmosis-cats
Toxoplasmosis is a disease caused by the single-celled parasite Toxoplasma gondii (T. gondii). It is one of the most common parasitic diseases and infects nearly all warm-blooded animals, including pets and humans. […] The life cycle of T. gondii is complex and involves two types of hosts definitive hosts in which the parasite reproduces and forms eggs (called oocysts), and intermediate hosts in which it reproduces by making clones of itself, which cluster inside cysts. Wild and domestic cats are the only definitive hosts for T. gondii. When a cat ingests infected prey or raw meat, the parasite is released from cysts into the cats digestive tract, where it reproduces and produces oocysts. […] Additionally, some of the T. gondii released from cysts from the infected meat will penetrate more deeply into the wall of the cats intestine and multiply as yet another form, called a tachyzoite. This form then spreads from the intestine to other parts of the cat. Eventually, the cats immune system forces the parasite into a dormant or resting stage where it forms cysts in muscles and the brain. These cysts contain slowly multiplying Toxoplasma organisms in yet another form, called a bradyzoite.
#7 Toxoplasmosis: Background, Etiology and Pathophysiology, Epidemiology
https://emedicine.medscape.com/article/229969-overview
Toxoplasmosis is caused by infection with the protozoan Toxoplasma gondii, an obligate intracellular parasite. The infection produces a wide range of clinical syndromes in humans, land and sea mammals, and various bird species. T gondii has been recovered from locations throughout the world, except Antarctica. […] There are 3 major genotypes (type I, type II, and type III) of T gondii. These genotypes differ in their pathogenicity and prevalence in people. In Europe and the United States, type II genotype is responsible for most cases of congenital toxoplasmosis. […] T gondii infects a large proportion of the world’s population (perhaps one third) but uncommonly causes clinically significant disease. However, certain individuals are at high risk for severe or life-threatening toxoplasmosis. Individuals at risk for toxoplasmosis include fetuses, newborns, and immunologically impaired patients.
#8 Toxoplasmosis: Ocular disease – UpToDate
https://www.uptodate.com/contents/toxoplasmosis-ocular-disease/print
Toxoplasmosis, an infection with a worldwide distribution, is caused by the intracellular protozoan parasite, Toxoplasma gondii. […] This topic will review the pathogenesis, clinical manifestations, diagnosis, and treatment of ocular toxoplasmosis. […] It is well established that T. gondii can be divided into different genotypes, which are prevalent in different geographic areas. The different genotypes differ in pathogenicity and can therefore impact the clinical presentation, severity, and course of disease as well as the risk for ocular recurrences of T. gondii infection. […] The three main T. gondii genotypes are types I, II, and III. In Europe and the United States, where genotype II is prevalent, 80 to 90 percent of individuals who become infected are asymptomatic. This is in contrast to South and Central America, where genotype I and atypical strains predominate, resulting in a substantially increased severity of clinical disease. […] As an example, T. gondii infection in South and Central America is associated with much higher rates of posterior uveitis compared with other geographic areas.
#9 Toxoplasmosis: Background, Etiology and Pathophysiology, Epidemiology
https://emedicine.medscape.com/article/229969-overview
Toxoplasmosis is caused by infection with the protozoan Toxoplasma gondii, an obligate intracellular parasite. The infection produces a wide range of clinical syndromes in humans, land and sea mammals, and various bird species. T gondii has been recovered from locations throughout the world, except Antarctica. […] There are 3 major genotypes (type I, type II, and type III) of T gondii. These genotypes differ in their pathogenicity and prevalence in people. In Europe and the United States, type II genotype is responsible for most cases of congenital toxoplasmosis. […] T gondii infects a large proportion of the world’s population (perhaps one third) but uncommonly causes clinically significant disease. However, certain individuals are at high risk for severe or life-threatening toxoplasmosis. Individuals at risk for toxoplasmosis include fetuses, newborns, and immunologically impaired patients.
#10 toxoplasmosis etiology pathogenesis and treatment | PPT
https://www.slideshare.net/slideshow/toxoplasmosis-etiology-pathogenesis-and-treatment/266889491
Toxoplasmosis has three morphological forms: trophozoite, tissue cyst, and oocyst. Trophozoites invade and replicate within host cells. Tissue cysts form during chronic infection and contain slowly multiplying bradyzoites. Oocysts only form in definitive hosts and are the infective form shed in feces. The life cycle involves sexual reproduction in cats/felines and asexual reproduction in intermediate hosts like humans. Congenital toxoplasmosis poses risks to fetuses and can cause issues like chorioretinitis. Diagnosis involves microscopic examination, isolation, and serology testing like ELISA and dye tests. […] Rapidly proliferating trophozoites called TACHYZOITES. […] Slowly multiplying parasites called BRADYZOITES tissue cyst. […] OOCYST Formed only in definitive host Infective form FORMATION: Cats on ingestion of tissue/oocyst develop parasites in intestinal epithelium.
#11 Toxoplasmosis in Cats | Cornell University College of Veterinary Medicine
https://www.vet.cornell.edu/departments-centers-and-institutes/cornell-feline-health-center/health-information/feline-health-topics/toxoplasmosis-cats
Toxoplasmosis is a disease caused by the single-celled parasite Toxoplasma gondii (T. gondii). It is one of the most common parasitic diseases and infects nearly all warm-blooded animals, including pets and humans. […] The life cycle of T. gondii is complex and involves two types of hosts definitive hosts in which the parasite reproduces and forms eggs (called oocysts), and intermediate hosts in which it reproduces by making clones of itself, which cluster inside cysts. Wild and domestic cats are the only definitive hosts for T. gondii. When a cat ingests infected prey or raw meat, the parasite is released from cysts into the cats digestive tract, where it reproduces and produces oocysts. […] Additionally, some of the T. gondii released from cysts from the infected meat will penetrate more deeply into the wall of the cats intestine and multiply as yet another form, called a tachyzoite. This form then spreads from the intestine to other parts of the cat. Eventually, the cats immune system forces the parasite into a dormant or resting stage where it forms cysts in muscles and the brain. These cysts contain slowly multiplying Toxoplasma organisms in yet another form, called a bradyzoite.
#12 Ocular Toxoplasmosis: Overview, Pathogenesis, Congenital Versus Acquired Ocular Toxoplasmosis
https://emedicine.medscape.com/article/2044905-overview
Patients become infected with toxoplamosis by 3 main routes: 1) Eating contaminated undercooked meat containing tissue cysts; 2) Consuming contaminated food or water with oocysts; and 3) Transplacental transmission of tachyzoites to the fetus during primary maternal infection. […] Given these routes, one of the main sites where the parasite gains a foothold in the human body is the small intestine. From there, the parasite is carried by the bloodstream and the lymphatics. […] The main point of entry of the parasite into the posterior segment of the eye is the retinal circulation. Rarely, it may gain access through the choroidal circulation as evidenced by the cases of punctate outer retinal toxoplasmosis where the RPE and the outer retina are selectively affected. […] A recent mouse model of T gondii infection revealed that ferroptosis may be involved in the infection of photoreceptors during ocular toxoplasmosis.
#13 Toxoplasmosis: Background, Etiology and Pathophysiology, Epidemiology
https://emedicine.medscape.com/article/229969-overview
During a primary infection, the cat can excrete millions of oocysts daily for 1-3 weeks. The oocysts are very strong and may remain infectious for more than one year in warm humid environments. […] T gondii oocysts, tachyzoites, and bradyzoites can cause infection in humans. Infection can occur by ingestion of oocysts following the handling of contaminated soil or cat litter or through the consumption of contaminated water or food sources (eg, unwashed garden vegetables). […] The ability of T gondii to actively penetrate host cells results in formation of a parasitophorous vacuole that is derived from the plasma membrane, which is entirely distinct from a normal phagocytic or endocytic compartment. […] Following apical attachment, the parasite rapidly enters the host cell in a process that is significantly faster than phagocytosis. The vacuole is formed primarily by invagination of the host cell plasma membrane, which is pulled over the parasite through the concerted action of the actin-myosin cytoskeleton of the parasite.
#14 Toxoplasmosis pathophysiology – wikidoc
https://www.wikidoc.org/index.php/Toxoplasmosis_pathophysiology
Toxoplasma gondii is a protozoan parasite that infects most species of warm blooded animals, including humans, causing the disease toxoplasmosis. Members of the cat family (Felidae) are the only known definitive hosts for the sexual stages of T. gondii and thus are the main reservoirs of infection. Cats become infected with T. gondii by carnivorism. After tissue cysts or oocysts are ingested by the cat, viable organisms are released and invade epithelial cells of the small intestine where they undergo an asexual followed by a sexual cycle and then form oocysts, which are excreted. The unsporulated oocyst takes 1 to 5 days after excretion to sporulate (become infective). Although cats shed oocysts for only 1 to 2 weeks, large numbers may be shed. Oocysts can survive in the environment for several months and are remarkably resistant to disinfectants, freezing, and drying, but are killed by heating to 70C for 10 minutes.
#15 Toxoplasma Gondii – Medical Microbiology – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK7752/
Host cells are destroyed by active multiplication of T gondii. Necrotic foci may result. […] Most cases of toxoplasmosis in humans are probably acquired by the ingestion of either tissue cysts in infected meat or oocysts in food contaminated with cat feces. Bradyzoites from the tissue cysts or sporozoites released from oocysts penetrate the intestinal epithelial cells and multiply in the intestine. Toxoplasma gondii may spread both locally to mesenteric lymph nodes and to distant organs by invading the lymphatics and blood. Necrosis in intestinal and mesenteric lymph nodes may occur before other organs become severely damaged. Focal areas of necrosis may develop in many organs. The clinical picture is determined by the extent of injury to these organs, especially to vital and vulnerable organs such as the eye, heart, and adrenals. Toxoplasma gondii does not produce a toxin; necrosis is caused by intracellular multiplication of tachyzoites. […] Opportunistic toxoplasmosis in AIDS patients usually represents reactivation of chronic infection. The predominant lesion of toxoplasmosis – encephalitis in these patients is necrosis, which often results in multiple abscesses, some as large as a tennis ball.
#16 pathogenesis
https://kdna.net/parasite_course-old/toxo_files/subchapters/pathogenesis.htm
Most cases of toxoplasmosis in humans are acquired by ingestion of infected meat containing tissue cysts with bradyzoites or food contaminated with cat feces containing oocysts. Bradyzoites or sporozoites penetrate intestinal cells and then spread locally to the mesenteric lymph nodes and then to distant organs via the lymphatics and blood. […] Tissue death is not the result of a Toxoplasma toxin, but is a consequence of the egress of the tachyzoites which destroys the host cell. […] In the child of a woman who acquires the infection for the first time during pregnancy. […] Transplacental infections (by tachyzoites) results in: subclinical !! 60% encephalitis hydrocephalus 30% microcephalus retinochoroiditis abortion 10%. […] In the 1980’s toxoplasmosis became one of the opportunistic diseases associated with immunocompromised patients, such as AIDS patients, transplantation patients and cancer patients treated with immunosuppressive drugs. […] Reactivation probably results from rupture of the cyst and renewed multiplication of bradyzoites into tachyzoites.
#17 Mechanisms and pathways of Toxoplasma gondii transepithelial migration
https://pmc.ncbi.nlm.nih.gov/articles/PMC5362999/
The crucial step for T. gondii establishment of infection and subsequent parasite survival and proliferation is parasite attachment to, and transmigration of the intestinal epithelial barrier. The disease outcome of T. gondii infection is therefore highly dependent on parasite virulence, although surprisingly T. gondii population biology has identified a limited number of dominant strains. […] In silico approaches are being increasingly used to identify new genes of interest or genetic pathways. […] The transcellular or active penetration invasion mechanism has been well described for T. gondii tachyzoites, bradyzoites and sporozoites using various molecular and imaging-based techniques. […] Following transmigration of the SI epithelium, T. gondii is known to exploit the motility of infiltrating SI immune cells in a Trojan Horse-like mechanism to spread throughout the body to secondary sites of infection, such as the muscle tissues or brain.
#18 Mechanisms and pathways of Toxoplasma gondii transepithelial migration
https://pmc.ncbi.nlm.nih.gov/articles/PMC5362999/
Toxoplasma gondii is a ubiquitous parasite and a prevalent food-borne parasitic pathogen. Infection of the host occurs principally through oral consumption of contaminated food and water with the gastrointestinal tract being the primary route for entry into the host. To promote infection, T. gondii has evolved highly specialized strategies for rapid traversal of the single cell thick intestinal epithelial barrier. Parasite transmigration via the paracellular pathway between adjacent cells enables parasite dissemination to secondary sites of infection where chronic infection of muscle and brain tissue is established. […] It is unclear currently, how T. gondii transmigrate the intestinal epithelium though it is essential for understanding disease pathogenesis. This review aims to build an understanding of how the success of T. gondii in global pathogenesis is linked with its ability to rapidly cross the epithelial barrier of the small intestine (SI), and to provide insights into how technological advances have enabled in-depth examination of how T. gondii interacts with the host cell, potentiating the design of novel intervention and protection strategies.
#19 Mechanisms and pathways of Toxoplasma gondii transepithelial migration
https://pmc.ncbi.nlm.nih.gov/articles/PMC5362999/
Toxoplasma gondii is a ubiquitous parasite and a prevalent food-borne parasitic pathogen. Infection of the host occurs principally through oral consumption of contaminated food and water with the gastrointestinal tract being the primary route for entry into the host. To promote infection, T. gondii has evolved highly specialized strategies for rapid traversal of the single cell thick intestinal epithelial barrier. Parasite transmigration via the paracellular pathway between adjacent cells enables parasite dissemination to secondary sites of infection where chronic infection of muscle and brain tissue is established. […] It is unclear currently, how T. gondii transmigrate the intestinal epithelium though it is essential for understanding disease pathogenesis. This review aims to build an understanding of how the success of T. gondii in global pathogenesis is linked with its ability to rapidly cross the epithelial barrier of the small intestine (SI), and to provide insights into how technological advances have enabled in-depth examination of how T. gondii interacts with the host cell, potentiating the design of novel intervention and protection strategies.
#20 Ocular Toxoplasmosis: Mechanisms of Retinal Infection and Experimental Models
https://www.mdpi.com/2673-6772/1/2/7
Once T. gondii has established infection in the small intestine, tachyzoites enter the draining blood and lymph travelling to remote sites as free bodies in the circulation, or inside leukocytes. […] Different histopathological and clinical observations show that T. gondii tachyzoites enter the eye via the blood supply that reaches the retina through the choroidal vessels, which irrigate the photoreceptors located in the outer retina, or through the retinal vessels entering at the optic nerve head, which irrigate the inner retina. […] Three possible routes have been identified for the passage of tachyzoites across the retinal endothelium: (a) Leukocyte transport. (b) Free parasite through a paracellular route. (c) Endothelial cell infection. […] It has been shown previously that monocytes are responsible for the arrival of T. gondii to the brain. In addition, recent studies have shown that even though all dendritic cells (DCs) transmigrate through the retinal endothelium, those infected by T. gondii display hypermotility and, therefore, better capacity to transmigrate compared to uninfected ones.
#21 Ocular Toxoplasmosis: Mechanisms of Retinal Infection and Experimental Models
https://www.mdpi.com/2673-6772/1/2/7
Once T. gondii has established infection in the small intestine, tachyzoites enter the draining blood and lymph travelling to remote sites as free bodies in the circulation, or inside leukocytes. […] Different histopathological and clinical observations show that T. gondii tachyzoites enter the eye via the blood supply that reaches the retina through the choroidal vessels, which irrigate the photoreceptors located in the outer retina, or through the retinal vessels entering at the optic nerve head, which irrigate the inner retina. […] Three possible routes have been identified for the passage of tachyzoites across the retinal endothelium: (a) Leukocyte transport. (b) Free parasite through a paracellular route. (c) Endothelial cell infection. […] It has been shown previously that monocytes are responsible for the arrival of T. gondii to the brain. In addition, recent studies have shown that even though all dendritic cells (DCs) transmigrate through the retinal endothelium, those infected by T. gondii display hypermotility and, therefore, better capacity to transmigrate compared to uninfected ones.
#22 Ocular Toxoplasmosis: Mechanisms of Retinal Infection and Experimental Models
https://www.mdpi.com/2673-6772/1/2/7
The mechanism allowing tachyzoites to move through a paracellular route is likely to involve an interaction with cell adhesion and intercellular tight junction molecules. […] Tachyzoites can remain infectious and survive outside host cells during long periods while maintaining the ability to adhere to the retinal endothelium. […] Recent studies in which T. gondii tachyzoites were cultivated in different human endothelial cell lines (retinal, aortic, umbilical vein, and dermal microvasculature) showed that retinal endothelial cells were the most susceptible to infection, showing a tachyzoite growth rate three times faster than that of dermal fibroblasts. […] The RPE upregulates the expression of major histocompatibility complex (MHC) class I and class II to present parasite antigens in the eye.
#23 Toxoplasmosis: Background, Etiology and Pathophysiology, Epidemiology
https://emedicine.medscape.com/article/229969-overview
During a primary infection, the cat can excrete millions of oocysts daily for 1-3 weeks. The oocysts are very strong and may remain infectious for more than one year in warm humid environments. […] T gondii oocysts, tachyzoites, and bradyzoites can cause infection in humans. Infection can occur by ingestion of oocysts following the handling of contaminated soil or cat litter or through the consumption of contaminated water or food sources (eg, unwashed garden vegetables). […] The ability of T gondii to actively penetrate host cells results in formation of a parasitophorous vacuole that is derived from the plasma membrane, which is entirely distinct from a normal phagocytic or endocytic compartment. […] Following apical attachment, the parasite rapidly enters the host cell in a process that is significantly faster than phagocytosis. The vacuole is formed primarily by invagination of the host cell plasma membrane, which is pulled over the parasite through the concerted action of the actin-myosin cytoskeleton of the parasite.
#24 Toxoplasmosis: Background, Etiology and Pathophysiology, Epidemiology
https://emedicine.medscape.com/article/229969-overview
During a primary infection, the cat can excrete millions of oocysts daily for 1-3 weeks. The oocysts are very strong and may remain infectious for more than one year in warm humid environments. […] T gondii oocysts, tachyzoites, and bradyzoites can cause infection in humans. Infection can occur by ingestion of oocysts following the handling of contaminated soil or cat litter or through the consumption of contaminated water or food sources (eg, unwashed garden vegetables). […] The ability of T gondii to actively penetrate host cells results in formation of a parasitophorous vacuole that is derived from the plasma membrane, which is entirely distinct from a normal phagocytic or endocytic compartment. […] Following apical attachment, the parasite rapidly enters the host cell in a process that is significantly faster than phagocytosis. The vacuole is formed primarily by invagination of the host cell plasma membrane, which is pulled over the parasite through the concerted action of the actin-myosin cytoskeleton of the parasite.
#25 Toxoplasma gondii – Wikipedia
https://en.wikipedia.org/wiki/Toxoplasma_gondii
Toxoplasma gondii is a species of parasitic alveolate that causes toxoplasmosis. Found worldwide, T. gondii is capable of infecting virtually all warm-blooded animals, but members of the cat family (felidae) are the only known definitive hosts in which the parasite may undergo sexual reproduction. […] The primary mechanisms of T. gondii induced behavioral changes in rodents occur through epigenetic remodeling in neurons that govern the relevant behaviors (e.g. hypomethylation of arginine vasopressin-related genes in the medial amygdala, which greatly decrease predator aversion). […] T. gondii contains organelles called rhoptries and micronemes. They contain proteins for invasion and effectors for manipulating the host’s immune response. To inject them into host cells, T. gondii uses the apical complex located in the tip of the cell to puncture the host membrane and discharge the contents of these organelles.
#26 Toxoplasma gondii – Wikipedia
https://en.wikipedia.org/wiki/Toxoplasma_gondii
Inside host cells, the tachyzoites replicate inside specialized vacuoles (called the parasitophorous vacuoles) created from host cell membrane during invasion into the cell. Tachyzoites multiply inside this vacuole until the host cell dies and ruptures, releasing and spreading the tachyzoites via the bloodstream to all organs and tissues of the body, including the brain. […] Following the initial period of infection characterized by tachyzoite proliferation throughout the body, pressure from the host’s immune system causes T. gondii tachyzoites to convert into bradyzoites, the semi-dormant, slowly dividing cellular stage of the parasite. […] The IFN–mediated activation of IDO and TDO is an evolutionary mechanism that serves to starve the parasite, but it can result in depletion of tryptophan in the brain of the host.
#27 Toxoplasmosis – Wikipedia
https://en.wikipedia.org/wiki/Toxoplasmosis
Toxoplasmosis is a parasitic disease caused by Toxoplasma gondii, an apicomplexan. Infections with toxoplasmosis are associated with a variety of neuropsychiatric and behavioral conditions. The parasite’s survival is dependent on a balance between host survival and parasite proliferation. T. gondii achieves this balance by manipulating the host’s immune response, reducing the host’s immune response, and enhancing the parasite’s reproductive advantage. Once it infects a normal host cell, it resists damage caused by the host’s immune system, and changes the host’s immune processes. As it forces its way into the host cell, the parasite forms a parasitophorous vacuole (PV) membrane from the membrane of the host cell. The PV encapsulates the parasite, and is both resistant to the activity of the endolysosomal system, and can take control of the host’s mitochondria and endoplasmic reticulum. When first invading the cell, the parasite releases ROP proteins from the bulb of the rhoptry organelle. These proteins translocate to the nucleus and the surface of the PV membrane where they can activate STAT pathways to modulate the expression of cytokines at the transcriptional level, bind and inactivate PV membrane destroying IRG proteins, among other possible effects. Additionally, certain strains of T. gondii can secrete a protein known as GRA15, activating the NF-B pathway, which upregulates the pro-inflammatory cytokine IL-12 in the early immune response, possibly leading to the parasite’s latent phase. The parasite’s ability to secrete these proteins depends on its genotype and affects its virulence. The parasite also influences an anti-apoptotic mechanism, allowing the infected host cells to persist and replicate. One method of apoptosis resistance is by disrupting pro-apoptosis effector proteins, such as BAX and BAK. To disrupt these proteins, T. gondii causes conformational changes to the proteins, which prevent the proteins from being transported to various cellular compartments where they initiate apoptosis events. T. gondii also has the ability to initiate autophagy of the host’s cells. This leads to a decrease in healthy, uninfected cells, and consequently fewer host cells to attack the infected cells. Research by Wang et al finds that infected cells lead to higher levels of autophagosomes in normal and infected cells. Their research reveals that T. gondii causes host cell autophagy using a calcium-dependent pathway. Another study suggests that the parasite can directly affect calcium being released from calcium stores, which are important for the signalling processes of cells. The mechanisms above allow T. gondii to persist in a host. Some limiting factors for the toxoplasma is that its influence on the host cells is stronger in a weak immune system and is quantity-dependent, so a large number of T. gondii per host cell cause a more severe effect. The effect on the host also depends on the strength of the host immune system. Immunocompetent individuals do not normally show severe symptoms or any at all, while fatality or severe complications can result in immunocompromised individuals. T. gondii has been shown to produce a protein called GRA28, released by the MYR1 secretory pathway, which interferes with gene expression in infected cells and results in cells that behave like dendritic cells, becoming highly mobile in the body. Since the parasite can change the host’s immune response, it may also have an effect, positive or negative, on the immune response to other pathogenic threats. This includes, but is not limited to, the responses to infections by Helicobacter felis, Leishmania major, or other parasites, such as Nippostrongylus brasiliensis.
#28 Toxoplasmosis – Wikipedia
https://en.wikipedia.org/wiki/Toxoplasmosis
Toxoplasmosis is a parasitic disease caused by Toxoplasma gondii, an apicomplexan. Infections with toxoplasmosis are associated with a variety of neuropsychiatric and behavioral conditions. The parasite’s survival is dependent on a balance between host survival and parasite proliferation. T. gondii achieves this balance by manipulating the host’s immune response, reducing the host’s immune response, and enhancing the parasite’s reproductive advantage. Once it infects a normal host cell, it resists damage caused by the host’s immune system, and changes the host’s immune processes. As it forces its way into the host cell, the parasite forms a parasitophorous vacuole (PV) membrane from the membrane of the host cell. The PV encapsulates the parasite, and is both resistant to the activity of the endolysosomal system, and can take control of the host’s mitochondria and endoplasmic reticulum. When first invading the cell, the parasite releases ROP proteins from the bulb of the rhoptry organelle. These proteins translocate to the nucleus and the surface of the PV membrane where they can activate STAT pathways to modulate the expression of cytokines at the transcriptional level, bind and inactivate PV membrane destroying IRG proteins, among other possible effects. Additionally, certain strains of T. gondii can secrete a protein known as GRA15, activating the NF-B pathway, which upregulates the pro-inflammatory cytokine IL-12 in the early immune response, possibly leading to the parasite’s latent phase. The parasite’s ability to secrete these proteins depends on its genotype and affects its virulence. The parasite also influences an anti-apoptotic mechanism, allowing the infected host cells to persist and replicate. One method of apoptosis resistance is by disrupting pro-apoptosis effector proteins, such as BAX and BAK. To disrupt these proteins, T. gondii causes conformational changes to the proteins, which prevent the proteins from being transported to various cellular compartments where they initiate apoptosis events. T. gondii also has the ability to initiate autophagy of the host’s cells. This leads to a decrease in healthy, uninfected cells, and consequently fewer host cells to attack the infected cells. Research by Wang et al finds that infected cells lead to higher levels of autophagosomes in normal and infected cells. Their research reveals that T. gondii causes host cell autophagy using a calcium-dependent pathway. Another study suggests that the parasite can directly affect calcium being released from calcium stores, which are important for the signalling processes of cells. The mechanisms above allow T. gondii to persist in a host. Some limiting factors for the toxoplasma is that its influence on the host cells is stronger in a weak immune system and is quantity-dependent, so a large number of T. gondii per host cell cause a more severe effect. The effect on the host also depends on the strength of the host immune system. Immunocompetent individuals do not normally show severe symptoms or any at all, while fatality or severe complications can result in immunocompromised individuals. T. gondii has been shown to produce a protein called GRA28, released by the MYR1 secretory pathway, which interferes with gene expression in infected cells and results in cells that behave like dendritic cells, becoming highly mobile in the body. Since the parasite can change the host’s immune response, it may also have an effect, positive or negative, on the immune response to other pathogenic threats. This includes, but is not limited to, the responses to infections by Helicobacter felis, Leishmania major, or other parasites, such as Nippostrongylus brasiliensis.
#29 Molecular Mechanisms of Pathogenesis in Toxoplasma | National Agricultural Library
https://www.nal.usda.gov/research-tools/food-safety-research-projects/molecular-mechanisms-pathogenesis-toxoplasma
My long-term research goal is to study the mechanisms of virulence in the intracellular pathogen Toxoplasma gondii, and determine the role of parasite strain type in determining disease outcome. […] While the effect of ROP18 on virulence in mice is clear, its mechanism of action is poorly understood, and it is the goal of this project to determine the molecular and cellular mechanisms for the impact of ROP18 on virulence. […] These approaches should yield new insights into the molecular targets of ROP18 that are relevant to its effects on virulence, and increase our understanding of the mechanisms of virulence in general. […] The goal of this project is to understand why some strains of Toxoplasma cause more severe disease than others.
#30 Toxoplasma Gondii – Medical Microbiology – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK7752/
Host cells are destroyed by active multiplication of T gondii. Necrotic foci may result. […] Most cases of toxoplasmosis in humans are probably acquired by the ingestion of either tissue cysts in infected meat or oocysts in food contaminated with cat feces. Bradyzoites from the tissue cysts or sporozoites released from oocysts penetrate the intestinal epithelial cells and multiply in the intestine. Toxoplasma gondii may spread both locally to mesenteric lymph nodes and to distant organs by invading the lymphatics and blood. Necrosis in intestinal and mesenteric lymph nodes may occur before other organs become severely damaged. Focal areas of necrosis may develop in many organs. The clinical picture is determined by the extent of injury to these organs, especially to vital and vulnerable organs such as the eye, heart, and adrenals. Toxoplasma gondii does not produce a toxin; necrosis is caused by intracellular multiplication of tachyzoites. […] Opportunistic toxoplasmosis in AIDS patients usually represents reactivation of chronic infection. The predominant lesion of toxoplasmosis – encephalitis in these patients is necrosis, which often results in multiple abscesses, some as large as a tennis ball.
#31 Toxoplasma Gondii – Medical Microbiology – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK7752/
Host cells are destroyed by active multiplication of T gondii. Necrotic foci may result. […] Most cases of toxoplasmosis in humans are probably acquired by the ingestion of either tissue cysts in infected meat or oocysts in food contaminated with cat feces. Bradyzoites from the tissue cysts or sporozoites released from oocysts penetrate the intestinal epithelial cells and multiply in the intestine. Toxoplasma gondii may spread both locally to mesenteric lymph nodes and to distant organs by invading the lymphatics and blood. Necrosis in intestinal and mesenteric lymph nodes may occur before other organs become severely damaged. Focal areas of necrosis may develop in many organs. The clinical picture is determined by the extent of injury to these organs, especially to vital and vulnerable organs such as the eye, heart, and adrenals. Toxoplasma gondii does not produce a toxin; necrosis is caused by intracellular multiplication of tachyzoites. […] Opportunistic toxoplasmosis in AIDS patients usually represents reactivation of chronic infection. The predominant lesion of toxoplasmosis – encephalitis in these patients is necrosis, which often results in multiple abscesses, some as large as a tennis ball.
#32 pathogenesis
https://kdna.net/parasite_course-old/toxo_files/subchapters/pathogenesis.htm
Most cases of toxoplasmosis in humans are acquired by ingestion of infected meat containing tissue cysts with bradyzoites or food contaminated with cat feces containing oocysts. Bradyzoites or sporozoites penetrate intestinal cells and then spread locally to the mesenteric lymph nodes and then to distant organs via the lymphatics and blood. […] Tissue death is not the result of a Toxoplasma toxin, but is a consequence of the egress of the tachyzoites which destroys the host cell. […] In the child of a woman who acquires the infection for the first time during pregnancy. […] Transplacental infections (by tachyzoites) results in: subclinical !! 60% encephalitis hydrocephalus 30% microcephalus retinochoroiditis abortion 10%. […] In the 1980’s toxoplasmosis became one of the opportunistic diseases associated with immunocompromised patients, such as AIDS patients, transplantation patients and cancer patients treated with immunosuppressive drugs. […] Reactivation probably results from rupture of the cyst and renewed multiplication of bradyzoites into tachyzoites.
#33 Toxoplasmosis: Background, Etiology and Pathophysiology, Epidemiology
https://emedicine.medscape.com/article/229969-overview
Tachyzoites proliferate, producing necrotic foci surrounded by a cellular reaction. Upon the development of a normal immune response, tachyzoites disappear from tissues. In immunodeficient individuals and in some apparently immunologically healthy patients, the acute infection progresses, resulting in potentially lethal consequences such as pneumonitis, myocarditis, and necrotizing encephalitis. […] Tissue cysts form as early as 7 days after infection and remain for the lifespan of the host. The tissue cysts are up to 60m in diameter, each containing up to 60,000 organisms. They produce little or no inflammatory response but cause recrudescent disease in immunocompromised patients or retinochoroiditis in congenitally infected older children. […] Alterations in subpopulations of T lymphocytes are profound and prolonged during acute acquired T gondii infection. These have been correlated with disease syndromes but not with disease outcome.
#34 Toxoplasmosis – WikiLectures
https://www.wikilectures.eu/w/Toxoplasmosis
After ingestion of oocysts, bradyzoites or sporozoites begin to release and enter the host (nuclear) cells of the digestive tract. The tachyzoites divide within the host cell until the cell ruptures and the tachyzoites infect neighboring cells. They spread through the lymph and disseminate hematogenously through the tissues. […] Tachyzoites proliferate, forming necrotic deposits surrounded by a cellular response. As the normal immune response develops, the tachyzoites disappear from the tissues. In immunocompromised patients, acute infections may progress further and result in pneumonia, myocarditis, and necrotizing encephalitis. […] Tissue cysts form as early as 7 days after infection and remain throughout the host’s life. It produces very little or no immune response.
#35 Toxoplasmosis: Background, Etiology and Pathophysiology, Epidemiology
https://emedicine.medscape.com/article/229969-overview
Tachyzoites proliferate, producing necrotic foci surrounded by a cellular reaction. Upon the development of a normal immune response, tachyzoites disappear from tissues. In immunodeficient individuals and in some apparently immunologically healthy patients, the acute infection progresses, resulting in potentially lethal consequences such as pneumonitis, myocarditis, and necrotizing encephalitis. […] Tissue cysts form as early as 7 days after infection and remain for the lifespan of the host. The tissue cysts are up to 60m in diameter, each containing up to 60,000 organisms. They produce little or no inflammatory response but cause recrudescent disease in immunocompromised patients or retinochoroiditis in congenitally infected older children. […] Alterations in subpopulations of T lymphocytes are profound and prolonged during acute acquired T gondii infection. These have been correlated with disease syndromes but not with disease outcome.
#36 Toxoplasmosis: Background, Etiology and Pathophysiology, Epidemiology
https://emedicine.medscape.com/article/229969-overview
Tachyzoites proliferate, producing necrotic foci surrounded by a cellular reaction. Upon the development of a normal immune response, tachyzoites disappear from tissues. In immunodeficient individuals and in some apparently immunologically healthy patients, the acute infection progresses, resulting in potentially lethal consequences such as pneumonitis, myocarditis, and necrotizing encephalitis. […] Tissue cysts form as early as 7 days after infection and remain for the lifespan of the host. The tissue cysts are up to 60m in diameter, each containing up to 60,000 organisms. They produce little or no inflammatory response but cause recrudescent disease in immunocompromised patients or retinochoroiditis in congenitally infected older children. […] Alterations in subpopulations of T lymphocytes are profound and prolonged during acute acquired T gondii infection. These have been correlated with disease syndromes but not with disease outcome.
#37 Toxoplasmosis: Background, Etiology and Pathophysiology, Epidemiology
https://emedicine.medscape.com/article/229969-overview
The most significant manifestation of toxoplasmosis in the fetus is encephalomyelitis, which may have severe results. […] Most cases of toxoplasmosis in immunocompromised patients are a consequence of latent infection and reactivation. In patients with AIDS, T gondii tissue cysts can reactivate with CD4 counts of less than 200 cells/L; with counts of less than 100 cells/L, clinical disease becomes more likely. […] Chronic infection occurs 2 to 3 weeks after infection, when the production of cytokines and antibodies against many T gondii proteins begins. Extracellular tachyzoites are cleared from host tissues and intracellular parasites differentiate into occult bradyzoite forms surrounded by a parasitophore vacuole enclosed in a cyst wall.
#38 Toxoplasma gondii – Wikipedia
https://en.wikipedia.org/wiki/Toxoplasma_gondii
Inside host cells, the tachyzoites replicate inside specialized vacuoles (called the parasitophorous vacuoles) created from host cell membrane during invasion into the cell. Tachyzoites multiply inside this vacuole until the host cell dies and ruptures, releasing and spreading the tachyzoites via the bloodstream to all organs and tissues of the body, including the brain. […] Following the initial period of infection characterized by tachyzoite proliferation throughout the body, pressure from the host’s immune system causes T. gondii tachyzoites to convert into bradyzoites, the semi-dormant, slowly dividing cellular stage of the parasite. […] The IFN–mediated activation of IDO and TDO is an evolutionary mechanism that serves to starve the parasite, but it can result in depletion of tryptophan in the brain of the host.
#39 Companion Animal Parasite Council | Toxoplasma gondii
https://capcvet.org/guidelines/toxoplasma-gondii/
Toxoplasma gondii is a two-host coccidial organism, although cats can also be infected by the ingestion of oocysts. […] Sexual stages develop only in the intestine of felid definitive hosts (wild and domestic). […] Extraintestinal, asexual stages (tachyzoites, bradyzoites) develop in all mammalian and avian species. […] Tachyzoites divide rapidly within various cells, leading to cell death, tissue necrosis, and granulomatous inflammation. […] Following acute infection, the organism survives for extended periods in host tissues as slowly dividing bradyzoites within tissue cysts. Bradyzoites may be reactivated and transform to rapidly dividing tachyzoites upon host immunosuppression. […] Clinical disease is more severe in immunocompromised individuals, developing fetuses, and the elderly.
#40 pathogenesis
https://kdna.net/parasite_course-old/toxo_files/subchapters/pathogenesis.htm
Most cases of toxoplasmosis in humans are acquired by ingestion of infected meat containing tissue cysts with bradyzoites or food contaminated with cat feces containing oocysts. Bradyzoites or sporozoites penetrate intestinal cells and then spread locally to the mesenteric lymph nodes and then to distant organs via the lymphatics and blood. […] Tissue death is not the result of a Toxoplasma toxin, but is a consequence of the egress of the tachyzoites which destroys the host cell. […] In the child of a woman who acquires the infection for the first time during pregnancy. […] Transplacental infections (by tachyzoites) results in: subclinical !! 60% encephalitis hydrocephalus 30% microcephalus retinochoroiditis abortion 10%. […] In the 1980’s toxoplasmosis became one of the opportunistic diseases associated with immunocompromised patients, such as AIDS patients, transplantation patients and cancer patients treated with immunosuppressive drugs. […] Reactivation probably results from rupture of the cyst and renewed multiplication of bradyzoites into tachyzoites.
#41 CDC – DPDx – Toxoplasmosis
https://www.cdc.gov/dpdx/toxoplasmosis/index.html
Toxoplasma gondii is a protozoan parasite that infects most species of warm-blooded animals, including humans, and causes the disease toxoplasmosis. […] In the human host, the parasites form tissue cysts, most commonly in skeletal muscle, myocardium, brain, and eyes; these cysts may remain throughout the life of the host. […] Congenital toxoplasmosis results from an acute primary infection acquired by the mother during pregnancy. […] Ocular Toxoplasma infection, an important cause of retinochoroiditis in the United States, can be the result of congenital infection, or infection after birth. […] Toxoplasmosis in patients being treated with immunosuppressive drugs may be due to either newly acquired or reactivated latent infection. […] The diagnosis of toxoplasmosis may be documented by serologic testing, which is the routine method of diagnosis. […] Detection of parasite genetic material by PCR, especially in detecting congenital infections in utero and toxoplasmic encephalitis in people with HIV. […] The detection of Toxoplasma-specific antibodies is the primary diagnostic method to determine infection with Toxoplasma.
#42 Toxoplasmosis – Infectious Diseases – Merck Manual Professional Edition
https://www.merckmanuals.com/professional/infectious-diseases/extraintestinal-protozoa/toxoplasmosis
T. gondii is ubiquitous in birds and mammals. This obligate intracellular parasite invades and multiplies asexually as tachyzoites within the cytoplasm of any nucleated cell. When host immunity develops, multiplication of tachyzoites ceases and tissue cysts form; cysts persist in a dormant state for years, especially in brain, eyes, and muscle. The dormant Toxoplasma forms within the cysts are called bradyzoites. […] After ingestion of oocysts or tissue cysts, tachyzoites are released and spread throughout the body. This acute infection is followed by the development of protective immune responses and the formation of tissue cysts in many organs. The cysts can reactivate causing disease, primarily in immunocompromised patients. Toxoplasmosis reactivates in 30 to 40% of AIDS patients who are not taking antibiotic prophylaxis, but the widespread use of trimethoprim/sulfamethoxazole for Pneumocystis prophylaxis has dramatically reduced the incidence. […] In the human host, parasites form tissue cysts, most commonly in skeletal muscle, myocardium, the brain, and the eyes; these cysts may remain throughout the life of the host and can reactivate if the host becomes immunocompromised.
#43 Behavioral biology of Toxoplasma gondii infection | Parasites & Vectors | Full Text
https://parasitesandvectors.biomedcentral.com/articles/10.1186/s13071-020-04528-x
Toxoplasma gondii is a protozoan parasite with a complex life cycle and a cosmopolitan host range. […] The parasite changes the behavior of its intermediate hosts by reducing their innate fear to cat odors and thereby plausibly increasing the probability that the definitive host will devour the infected host. […] T. gondii manipulates the behavior of its host to increase its transmission. […] The rodent T. gondii model is, in fact, one of the most studied models of parasitic behavioral manipulation. […] The majority of genetic diversity found in T. gondii can be found in three clonal lineages. […] Toxoplasma gondii exhibits a decided tropism for the brain and eyes. […] Toxoplasma gondii infection also increases the synthesis of arginine vasopressin in a specific brain region called the medial amygdala.
#44 Toxoplasmosis: Background, Etiology and Pathophysiology, Epidemiology
https://emedicine.medscape.com/article/229969-overview
The most significant manifestation of toxoplasmosis in the fetus is encephalomyelitis, which may have severe results. […] Most cases of toxoplasmosis in immunocompromised patients are a consequence of latent infection and reactivation. In patients with AIDS, T gondii tissue cysts can reactivate with CD4 counts of less than 200 cells/L; with counts of less than 100 cells/L, clinical disease becomes more likely. […] Chronic infection occurs 2 to 3 weeks after infection, when the production of cytokines and antibodies against many T gondii proteins begins. Extracellular tachyzoites are cleared from host tissues and intracellular parasites differentiate into occult bradyzoite forms surrounded by a parasitophore vacuole enclosed in a cyst wall.
#45 Toxoplasmosis: Background, Etiology and Pathophysiology, Epidemiology
https://emedicine.medscape.com/article/229969-overview
The most significant manifestation of toxoplasmosis in the fetus is encephalomyelitis, which may have severe results. […] Most cases of toxoplasmosis in immunocompromised patients are a consequence of latent infection and reactivation. In patients with AIDS, T gondii tissue cysts can reactivate with CD4 counts of less than 200 cells/L; with counts of less than 100 cells/L, clinical disease becomes more likely. […] Chronic infection occurs 2 to 3 weeks after infection, when the production of cytokines and antibodies against many T gondii proteins begins. Extracellular tachyzoites are cleared from host tissues and intracellular parasites differentiate into occult bradyzoite forms surrounded by a parasitophore vacuole enclosed in a cyst wall.
#46
https://link.springer.com/article/10.1007/s11908-000-0016-x
In patients with HIV, Toxoplasma gondii is the most frequent infectious cause of focal brain lesions. […] Particularly in advanced HIV disease, it can cause significant morbidity and mortality. […] Current clinical practice involves empiric therapy with pyrimethamine and sulfadiazine, upon a presumptive diagnosis of toxoplasmic encephalitis, based on serologic, clinical, and radiological features. […] Primary and secondary prophylaxis are the mainstay of treatment. […] There remains a continuing need for development of new anti-Toxoplasma therapy.
#47 Toxoplasmosis: identification of a mechanism ensuring the immune surveillance of infection in the brain – Inserm Newsroom
https://presse.inserm.fr/en/toxoplasmose-identification-dun-mecanisme-assurant-la-surveillance-immunitaire-de-linfection-dans-le-cerveau/68699/
The research team had previously shown that specific immune cells, called CD8+ T cells or killer T cells, play a key role in controlling the parasite in the brain. […] For Inserm researcher Nicolas Blanchard and his team, it was crucial to identify which CD8+ T-cell subtype is involved, in order to elucidate the immune surveillance mechanisms of the parasite in the brain. […] The role of the brain-resident CD8+ T cell subpopulations in neutralising and eliminating the parasite had never previously been studied. […] Through selective elimination of the circulating or resident subpopulations, the team showed that the parasite is controlled in the brain by resident CD8+ T cells, as opposed to the other lymphocytes that patrol the lymphoid organs and tissues. […] The researchers have also shown that the resident CD8+ T cells form thanks to signals issued by other immune cells, namely CD4+ T cells.
#48 CDC – DPDx – Toxoplasmosis
https://www.cdc.gov/dpdx/toxoplasmosis/index.html
Toxoplasma gondii is a protozoan parasite that infects most species of warm-blooded animals, including humans, and causes the disease toxoplasmosis. […] In the human host, the parasites form tissue cysts, most commonly in skeletal muscle, myocardium, brain, and eyes; these cysts may remain throughout the life of the host. […] Congenital toxoplasmosis results from an acute primary infection acquired by the mother during pregnancy. […] Ocular Toxoplasma infection, an important cause of retinochoroiditis in the United States, can be the result of congenital infection, or infection after birth. […] Toxoplasmosis in patients being treated with immunosuppressive drugs may be due to either newly acquired or reactivated latent infection. […] The diagnosis of toxoplasmosis may be documented by serologic testing, which is the routine method of diagnosis. […] Detection of parasite genetic material by PCR, especially in detecting congenital infections in utero and toxoplasmic encephalitis in people with HIV. […] The detection of Toxoplasma-specific antibodies is the primary diagnostic method to determine infection with Toxoplasma.
#49 Ocular Toxoplasmosis: Overview, Pathogenesis, Congenital Versus Acquired Ocular Toxoplasmosis
https://emedicine.medscape.com/article/2044905-overview
Patients become infected with toxoplamosis by 3 main routes: 1) Eating contaminated undercooked meat containing tissue cysts; 2) Consuming contaminated food or water with oocysts; and 3) Transplacental transmission of tachyzoites to the fetus during primary maternal infection. […] Given these routes, one of the main sites where the parasite gains a foothold in the human body is the small intestine. From there, the parasite is carried by the bloodstream and the lymphatics. […] The main point of entry of the parasite into the posterior segment of the eye is the retinal circulation. Rarely, it may gain access through the choroidal circulation as evidenced by the cases of punctate outer retinal toxoplasmosis where the RPE and the outer retina are selectively affected. […] A recent mouse model of T gondii infection revealed that ferroptosis may be involved in the infection of photoreceptors during ocular toxoplasmosis.
#50 Morphological characteristics of ocular toxoplasmosis and its regression pattern on swept-source optical coherence tomography angiography: a case report | BMC Ophthalmology | Full Text
https://bmcophthalmol.biomedcentral.com/articles/10.1186/s12886-019-1209-8
To report the successful treatment of ocular toxoplasmosis and present the use of multimodal imaging to describe the changes in ocular toxoplasmic lesions subsequent to treatment. […] Ocular toxoplasmosis is one of the most common cause of posterior uveitis caused by an intracellular parasite, Toxoplasma gondii. […] Following invasion of the parasite into the eye, the tachyzoite remains latent in the cyst under the control of the immune response of host. In event of trigger of rupture, the tachyzoite is converted to bradyzoite, and the inflammatory response is activated. […] Active inflammation tends to regress over few months with scar formation, and reactivation adjacent to old scar lesion is commonly observed in ocular toxoplasmosis. […] However, detailed morphological changes of the choroidal vasculature occurring from the active phase of the disease to remission after treatment using swept-source OCT-A (SS-OCT-A) have not yet been investigated.
#51 Ocular Toxoplasmosis: Overview, Pathogenesis, Congenital Versus Acquired Ocular Toxoplasmosis
https://emedicine.medscape.com/article/2044905-overview
Patients become infected with toxoplamosis by 3 main routes: 1) Eating contaminated undercooked meat containing tissue cysts; 2) Consuming contaminated food or water with oocysts; and 3) Transplacental transmission of tachyzoites to the fetus during primary maternal infection. […] Given these routes, one of the main sites where the parasite gains a foothold in the human body is the small intestine. From there, the parasite is carried by the bloodstream and the lymphatics. […] The main point of entry of the parasite into the posterior segment of the eye is the retinal circulation. Rarely, it may gain access through the choroidal circulation as evidenced by the cases of punctate outer retinal toxoplasmosis where the RPE and the outer retina are selectively affected. […] A recent mouse model of T gondii infection revealed that ferroptosis may be involved in the infection of photoreceptors during ocular toxoplasmosis.
#52 Morphological characteristics of ocular toxoplasmosis and its regression pattern on swept-source optical coherence tomography angiography: a case report | BMC Ophthalmology | Full Text
https://bmcophthalmol.biomedcentral.com/articles/10.1186/s12886-019-1209-8
The present study suggests that choroidal evaluation using en face SS-OCT and SS-OCT-A is useful for monitoring disease activity and may contribute substantially to therapeutic decision making in patients with ocular toxoplasmosis. […] The aim of the treatment was to arrest multiplication of the parasite during the active stage and to minimize damage to the intraocular tissues. […] The classical chemotherapeutic regimen for toxoplasmic retinochoroitidis consists of pyrimethamine and sulfadiazine, plus corticosteroids. […] A combination of Trimethoprim/sulfamethoxazole plus oral prednisolone has been suggested as an alternative treatment option with similar efficacy in terms of reduction in size of the retinal lesion and improvement in vision when compared with the classical therapy. […] In conclusion, multimodal imaging with SS-OCT and OCT-A was useful in evaluation of retinal and choroidal morphological characteristics in active toxoplasmic retinochoroiditis. In particular, en face SS-OCT images appears to be a valuable modality to elucidate the mechanism of structural changes in the choroid in patients with ocular toxoplasmosis.
#53 CDC – DPDx – Toxoplasmosis
https://www.cdc.gov/dpdx/toxoplasmosis/index.html
Toxoplasma gondii is a protozoan parasite that infects most species of warm-blooded animals, including humans, and causes the disease toxoplasmosis. […] In the human host, the parasites form tissue cysts, most commonly in skeletal muscle, myocardium, brain, and eyes; these cysts may remain throughout the life of the host. […] Congenital toxoplasmosis results from an acute primary infection acquired by the mother during pregnancy. […] Ocular Toxoplasma infection, an important cause of retinochoroiditis in the United States, can be the result of congenital infection, or infection after birth. […] Toxoplasmosis in patients being treated with immunosuppressive drugs may be due to either newly acquired or reactivated latent infection. […] The diagnosis of toxoplasmosis may be documented by serologic testing, which is the routine method of diagnosis. […] Detection of parasite genetic material by PCR, especially in detecting congenital infections in utero and toxoplasmic encephalitis in people with HIV. […] The detection of Toxoplasma-specific antibodies is the primary diagnostic method to determine infection with Toxoplasma.
#54 toxoplasmosis etiology pathogenesis and treatment | PPT
https://www.slideshare.net/slideshow/toxoplasmosis-etiology-pathogenesis-and-treatment/266889491
oocyst shed in feaces develop into infective form in soil ingested by felines ingested by int.host repeat cycle sporozoites release form tachyzoites causes infection. […] Risk of foetal infection: 25% – I trimester; severity is high 65% – III trimester Chorioretinitis, strabismus, blindness, deafness, hydrocephalus, microcephaly, MR, epilepsy, cerebral calcification, glaucoma, pneumonitis, myocarditis, HSM etc. […] Avidity of IgG antibodies against T. gondii thus, is a useful marker to differentiate between recent and remote infection.
#55 Toxoplasmosis in Animals – Generalized Conditions – Merck Veterinary Manual
https://www.merckvetmanual.com/generalized-conditions/toxoplasmosis/toxoplasmosis-in-animals
Toxoplasmosis is an important zoonotic protozoal infection worldwide. […] Toxoplasmosis is diagnosed by biologic, serologic, or histologic methods; or some combination of these. […] The tachyzoite is the stage responsible for tissue damage in toxoplasmosis; therefore, clinical signs depend on the affected tissue, the number of tachyzoites released, and the ability of the host immune system to limit replication and transmission. […] Tachyzoites infect tissues throughout the body and replicate intracellularly until the cells burst, causing tissue necrosis. […] Tachyzoites may also be transmitted to the fetus, causing necrosis in multiple organs. […] Toxoplasmosis is also a concern for pregnant women because tachyzoites can migrate transplacentally and cause neurologic disorders in the fetus.
#56 Toxoplasmosis pathophysiology – wikidoc
https://www.wikidoc.org/index.php/Toxoplasmosis_pathophysiology
The initial step of invasion is attachment of the tachyzoite to the host cell membrane. A set of proteins help in the adherence and penetration of the host cell membrane, these proteins also enhance the growth and virulence of the parasite. In the host cell the parasite forms a vacuole where it divides for 6 to 9 cycles after which the parasites are released into the circulation. It is an active process dependent on the increase in intracellular calcium stores. […] Acute infection with tachyzoites in the blood stream during pregnancy, a possibility of transplacental infection is present. The tachyzoites colonize in the placenta and can cross the barrier to reach the fetus in 30% of cases leading to the disease. The frequency of transmission of the tachyzoites to the fetus is related to the gestational age, with low transmission rates in the first trimester (10-15%) and highest transmission rates in the third trimester (60-90%). However the disease is more severe if the infection is acquired early in the pregnancy. The factors influencing the transfer of tachyzoites to the fetus is not well understood.
#57 Toxoplasmosis pathophysiology – wikidoc
https://www.wikidoc.org/index.php/Toxoplasmosis_pathophysiology
The initial step of invasion is attachment of the tachyzoite to the host cell membrane. A set of proteins help in the adherence and penetration of the host cell membrane, these proteins also enhance the growth and virulence of the parasite. In the host cell the parasite forms a vacuole where it divides for 6 to 9 cycles after which the parasites are released into the circulation. It is an active process dependent on the increase in intracellular calcium stores. […] Acute infection with tachyzoites in the blood stream during pregnancy, a possibility of transplacental infection is present. The tachyzoites colonize in the placenta and can cross the barrier to reach the fetus in 30% of cases leading to the disease. The frequency of transmission of the tachyzoites to the fetus is related to the gestational age, with low transmission rates in the first trimester (10-15%) and highest transmission rates in the third trimester (60-90%). However the disease is more severe if the infection is acquired early in the pregnancy. The factors influencing the transfer of tachyzoites to the fetus is not well understood.
#58 pathogenesis
https://kdna.net/parasite_course-old/toxo_files/subchapters/pathogenesis.htm
Most cases of toxoplasmosis in humans are acquired by ingestion of infected meat containing tissue cysts with bradyzoites or food contaminated with cat feces containing oocysts. Bradyzoites or sporozoites penetrate intestinal cells and then spread locally to the mesenteric lymph nodes and then to distant organs via the lymphatics and blood. […] Tissue death is not the result of a Toxoplasma toxin, but is a consequence of the egress of the tachyzoites which destroys the host cell. […] In the child of a woman who acquires the infection for the first time during pregnancy. […] Transplacental infections (by tachyzoites) results in: subclinical !! 60% encephalitis hydrocephalus 30% microcephalus retinochoroiditis abortion 10%. […] In the 1980’s toxoplasmosis became one of the opportunistic diseases associated with immunocompromised patients, such as AIDS patients, transplantation patients and cancer patients treated with immunosuppressive drugs. […] Reactivation probably results from rupture of the cyst and renewed multiplication of bradyzoites into tachyzoites.
#59 CDC – DPDx – Toxoplasmosis
https://www.cdc.gov/dpdx/toxoplasmosis/index.html
Toxoplasma gondii is a protozoan parasite that infects most species of warm-blooded animals, including humans, and causes the disease toxoplasmosis. […] In the human host, the parasites form tissue cysts, most commonly in skeletal muscle, myocardium, brain, and eyes; these cysts may remain throughout the life of the host. […] Congenital toxoplasmosis results from an acute primary infection acquired by the mother during pregnancy. […] Ocular Toxoplasma infection, an important cause of retinochoroiditis in the United States, can be the result of congenital infection, or infection after birth. […] Toxoplasmosis in patients being treated with immunosuppressive drugs may be due to either newly acquired or reactivated latent infection. […] The diagnosis of toxoplasmosis may be documented by serologic testing, which is the routine method of diagnosis. […] Detection of parasite genetic material by PCR, especially in detecting congenital infections in utero and toxoplasmic encephalitis in people with HIV. […] The detection of Toxoplasma-specific antibodies is the primary diagnostic method to determine infection with Toxoplasma.
#60 pathogenesis
https://kdna.net/parasite_course-old/toxo_files/subchapters/pathogenesis.htm
Most cases of toxoplasmosis in humans are acquired by ingestion of infected meat containing tissue cysts with bradyzoites or food contaminated with cat feces containing oocysts. Bradyzoites or sporozoites penetrate intestinal cells and then spread locally to the mesenteric lymph nodes and then to distant organs via the lymphatics and blood. […] Tissue death is not the result of a Toxoplasma toxin, but is a consequence of the egress of the tachyzoites which destroys the host cell. […] In the child of a woman who acquires the infection for the first time during pregnancy. […] Transplacental infections (by tachyzoites) results in: subclinical !! 60% encephalitis hydrocephalus 30% microcephalus retinochoroiditis abortion 10%. […] In the 1980’s toxoplasmosis became one of the opportunistic diseases associated with immunocompromised patients, such as AIDS patients, transplantation patients and cancer patients treated with immunosuppressive drugs. […] Reactivation probably results from rupture of the cyst and renewed multiplication of bradyzoites into tachyzoites.
#61 Toxoplasma Gondii – Medical Microbiology – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK7752/
Host cells are destroyed by active multiplication of T gondii. Necrotic foci may result. […] Most cases of toxoplasmosis in humans are probably acquired by the ingestion of either tissue cysts in infected meat or oocysts in food contaminated with cat feces. Bradyzoites from the tissue cysts or sporozoites released from oocysts penetrate the intestinal epithelial cells and multiply in the intestine. Toxoplasma gondii may spread both locally to mesenteric lymph nodes and to distant organs by invading the lymphatics and blood. Necrosis in intestinal and mesenteric lymph nodes may occur before other organs become severely damaged. Focal areas of necrosis may develop in many organs. The clinical picture is determined by the extent of injury to these organs, especially to vital and vulnerable organs such as the eye, heart, and adrenals. Toxoplasma gondii does not produce a toxin; necrosis is caused by intracellular multiplication of tachyzoites. […] Opportunistic toxoplasmosis in AIDS patients usually represents reactivation of chronic infection. The predominant lesion of toxoplasmosis – encephalitis in these patients is necrosis, which often results in multiple abscesses, some as large as a tennis ball.
#62 Toxoplasmosis in Cats | Cornell University College of Veterinary Medicine
https://www.vet.cornell.edu/departments-centers-and-institutes/cornell-feline-health-center/health-information/feline-health-topics/toxoplasmosis-cats
The prognosis for cats diagnosed with toxoplasmosis depends upon the organs or systems affected, the time between infection and treatment, and initial responses to therapy. […] Reducing the incidence of toxoplasmosis in cats requires measures to reduce both exposure to infective oocysts and shedding of oocysts into the environment. […] Pregnant women and immunodeficient individuals are the two populations most at risk of developing health problems after T. gondii exposure. […] In people who are either undergoing immunosuppressive therapy or have an immunosuppressive disease such as acquired immunodeficiency syndrome (AIDS), toxoplasmosis may cause enlargement of the lymph nodes, eye and central nervous system disturbances, respiratory disease, and heart disease. […] There is no vaccine to protect against toxoplasmosis in animals or humans.
#63 Toxoplasmosis – Wikipedia
https://en.wikipedia.org/wiki/Toxoplasmosis
Toxoplasmosis is a parasitic disease caused by Toxoplasma gondii, an apicomplexan. Infections with toxoplasmosis are associated with a variety of neuropsychiatric and behavioral conditions. The parasite’s survival is dependent on a balance between host survival and parasite proliferation. T. gondii achieves this balance by manipulating the host’s immune response, reducing the host’s immune response, and enhancing the parasite’s reproductive advantage. Once it infects a normal host cell, it resists damage caused by the host’s immune system, and changes the host’s immune processes. As it forces its way into the host cell, the parasite forms a parasitophorous vacuole (PV) membrane from the membrane of the host cell. The PV encapsulates the parasite, and is both resistant to the activity of the endolysosomal system, and can take control of the host’s mitochondria and endoplasmic reticulum. When first invading the cell, the parasite releases ROP proteins from the bulb of the rhoptry organelle. These proteins translocate to the nucleus and the surface of the PV membrane where they can activate STAT pathways to modulate the expression of cytokines at the transcriptional level, bind and inactivate PV membrane destroying IRG proteins, among other possible effects. Additionally, certain strains of T. gondii can secrete a protein known as GRA15, activating the NF-B pathway, which upregulates the pro-inflammatory cytokine IL-12 in the early immune response, possibly leading to the parasite’s latent phase. The parasite’s ability to secrete these proteins depends on its genotype and affects its virulence. The parasite also influences an anti-apoptotic mechanism, allowing the infected host cells to persist and replicate. One method of apoptosis resistance is by disrupting pro-apoptosis effector proteins, such as BAX and BAK. To disrupt these proteins, T. gondii causes conformational changes to the proteins, which prevent the proteins from being transported to various cellular compartments where they initiate apoptosis events. T. gondii also has the ability to initiate autophagy of the host’s cells. This leads to a decrease in healthy, uninfected cells, and consequently fewer host cells to attack the infected cells. Research by Wang et al finds that infected cells lead to higher levels of autophagosomes in normal and infected cells. Their research reveals that T. gondii causes host cell autophagy using a calcium-dependent pathway. Another study suggests that the parasite can directly affect calcium being released from calcium stores, which are important for the signalling processes of cells. The mechanisms above allow T. gondii to persist in a host. Some limiting factors for the toxoplasma is that its influence on the host cells is stronger in a weak immune system and is quantity-dependent, so a large number of T. gondii per host cell cause a more severe effect. The effect on the host also depends on the strength of the host immune system. Immunocompetent individuals do not normally show severe symptoms or any at all, while fatality or severe complications can result in immunocompromised individuals. T. gondii has been shown to produce a protein called GRA28, released by the MYR1 secretory pathway, which interferes with gene expression in infected cells and results in cells that behave like dendritic cells, becoming highly mobile in the body. Since the parasite can change the host’s immune response, it may also have an effect, positive or negative, on the immune response to other pathogenic threats. This includes, but is not limited to, the responses to infections by Helicobacter felis, Leishmania major, or other parasites, such as Nippostrongylus brasiliensis.
#64 Toxoplasmosis – Wikipedia
https://en.wikipedia.org/wiki/Toxoplasmosis
Toxoplasmosis is a parasitic disease caused by Toxoplasma gondii, an apicomplexan. Infections with toxoplasmosis are associated with a variety of neuropsychiatric and behavioral conditions. The parasite’s survival is dependent on a balance between host survival and parasite proliferation. T. gondii achieves this balance by manipulating the host’s immune response, reducing the host’s immune response, and enhancing the parasite’s reproductive advantage. Once it infects a normal host cell, it resists damage caused by the host’s immune system, and changes the host’s immune processes. As it forces its way into the host cell, the parasite forms a parasitophorous vacuole (PV) membrane from the membrane of the host cell. The PV encapsulates the parasite, and is both resistant to the activity of the endolysosomal system, and can take control of the host’s mitochondria and endoplasmic reticulum. When first invading the cell, the parasite releases ROP proteins from the bulb of the rhoptry organelle. These proteins translocate to the nucleus and the surface of the PV membrane where they can activate STAT pathways to modulate the expression of cytokines at the transcriptional level, bind and inactivate PV membrane destroying IRG proteins, among other possible effects. Additionally, certain strains of T. gondii can secrete a protein known as GRA15, activating the NF-B pathway, which upregulates the pro-inflammatory cytokine IL-12 in the early immune response, possibly leading to the parasite’s latent phase. The parasite’s ability to secrete these proteins depends on its genotype and affects its virulence. The parasite also influences an anti-apoptotic mechanism, allowing the infected host cells to persist and replicate. One method of apoptosis resistance is by disrupting pro-apoptosis effector proteins, such as BAX and BAK. To disrupt these proteins, T. gondii causes conformational changes to the proteins, which prevent the proteins from being transported to various cellular compartments where they initiate apoptosis events. T. gondii also has the ability to initiate autophagy of the host’s cells. This leads to a decrease in healthy, uninfected cells, and consequently fewer host cells to attack the infected cells. Research by Wang et al finds that infected cells lead to higher levels of autophagosomes in normal and infected cells. Their research reveals that T. gondii causes host cell autophagy using a calcium-dependent pathway. Another study suggests that the parasite can directly affect calcium being released from calcium stores, which are important for the signalling processes of cells. The mechanisms above allow T. gondii to persist in a host. Some limiting factors for the toxoplasma is that its influence on the host cells is stronger in a weak immune system and is quantity-dependent, so a large number of T. gondii per host cell cause a more severe effect. The effect on the host also depends on the strength of the host immune system. Immunocompetent individuals do not normally show severe symptoms or any at all, while fatality or severe complications can result in immunocompromised individuals. T. gondii has been shown to produce a protein called GRA28, released by the MYR1 secretory pathway, which interferes with gene expression in infected cells and results in cells that behave like dendritic cells, becoming highly mobile in the body. Since the parasite can change the host’s immune response, it may also have an effect, positive or negative, on the immune response to other pathogenic threats. This includes, but is not limited to, the responses to infections by Helicobacter felis, Leishmania major, or other parasites, such as Nippostrongylus brasiliensis.
#65 Exploring the potential of Toxoplasma gondii in drug development and as a delivery system | Experimental & Molecular Medicine
https://www.nature.com/articles/s12276-024-01165-7
Interestingly, to resist the immune response, T. gondii has successfully evolved strategies to evade the host immune system and migrate to immune-privileged sites, such as the CNS. T. gondii prevents the host immune system from entering through multiple mechanisms, including transcriptional regulation and interference with cell signaling, resulting in the secretion of inflammatory cytokines, modulation of matrix metalloproteases (MMPs), production of microbicidal molecules and apoptosis. […] T. gondii infection leads to anti-inflammatory cytokine production through an altered host immune system by manipulating host gene transcription and regulating signaling pathways. […] T. gondii has unique characteristics for drug delivery. T. gondii can infiltrate the BBB using immune cells, as in Trojan horses. Drug delivery via T. gondii employs immune cells that are involved in various diseases, and this approach might be applied to various diseases for which existing drug delivery has been difficult, including cancer.
#66 Behavioral biology of Toxoplasma gondii infection | Parasites & Vectors | Full Text
https://parasitesandvectors.biomedcentral.com/articles/10.1186/s13071-020-04528-x
Toxoplasma gondii is a protozoan parasite with a complex life cycle and a cosmopolitan host range. […] The parasite changes the behavior of its intermediate hosts by reducing their innate fear to cat odors and thereby plausibly increasing the probability that the definitive host will devour the infected host. […] T. gondii manipulates the behavior of its host to increase its transmission. […] The rodent T. gondii model is, in fact, one of the most studied models of parasitic behavioral manipulation. […] The majority of genetic diversity found in T. gondii can be found in three clonal lineages. […] Toxoplasma gondii exhibits a decided tropism for the brain and eyes. […] Toxoplasma gondii infection also increases the synthesis of arginine vasopressin in a specific brain region called the medial amygdala.
#67 Behavioral biology of Toxoplasma gondii infection | Parasites & Vectors | Full Text
https://parasitesandvectors.biomedcentral.com/articles/10.1186/s13071-020-04528-x
Toxoplasma gondii is a protozoan parasite with a complex life cycle and a cosmopolitan host range. […] The parasite changes the behavior of its intermediate hosts by reducing their innate fear to cat odors and thereby plausibly increasing the probability that the definitive host will devour the infected host. […] T. gondii manipulates the behavior of its host to increase its transmission. […] The rodent T. gondii model is, in fact, one of the most studied models of parasitic behavioral manipulation. […] The majority of genetic diversity found in T. gondii can be found in three clonal lineages. […] Toxoplasma gondii exhibits a decided tropism for the brain and eyes. […] Toxoplasma gondii infection also increases the synthesis of arginine vasopressin in a specific brain region called the medial amygdala.
#68 Toxoplasma gondii – Wikipedia
https://en.wikipedia.org/wiki/Toxoplasma_gondii
The mechanism behind behavioral changes is partially attributed to increased dopamine metabolism, which can be neutralized by dopamine antagonist medications. T. gondii has two genes that code for a bifunctional phenylalanine and tyrosine hydroxylase, two important and rate-limiting steps of dopamine biosynthesis.
#69 Stanley Medical Research Institute | Neurotransmitters and T. gondii
https://www.stanleyresearch.org/patient-and-provider-resources/toxoplasmosis-schizophrenia-research/neurotransmitters-and-t-gondii/
For more than 40 years, it has been known that neurotransmitters are involved in the pathogenesis of schizophrenia. […] Stibbs concluded that T. gondii causes abnormalities in catecholamine metabolism and that these may be factors contributing to the psychological and motor changes seen in experimentally infected rodents. […] In 2009, Dr. Glenn McConkey and his colleagues at the University of Leeds in the UK demonstrated that T. gondii has the genes encoding two critical enzymes needed to make dopamine. […] This finding suggests the possibility that the excess dopamine thought to occur in individuals with schizophrenia might be being introduced by T. gondii rather than made by the affected individuals. […] They speculated that possible explanatory mechanisms include the ability of haloperidol to inhibit T. gondii replication and to reduce, directly and indirectly, dopamine levels.
#70 Stanley Medical Research Institute | Neurotransmitters and T. gondii
https://www.stanleyresearch.org/patient-and-provider-resources/toxoplasmosis-schizophrenia-research/neurotransmitters-and-t-gondii/
For more than 40 years, it has been known that neurotransmitters are involved in the pathogenesis of schizophrenia. […] Stibbs concluded that T. gondii causes abnormalities in catecholamine metabolism and that these may be factors contributing to the psychological and motor changes seen in experimentally infected rodents. […] In 2009, Dr. Glenn McConkey and his colleagues at the University of Leeds in the UK demonstrated that T. gondii has the genes encoding two critical enzymes needed to make dopamine. […] This finding suggests the possibility that the excess dopamine thought to occur in individuals with schizophrenia might be being introduced by T. gondii rather than made by the affected individuals. […] They speculated that possible explanatory mechanisms include the ability of haloperidol to inhibit T. gondii replication and to reduce, directly and indirectly, dopamine levels.
#71 Stanley Medical Research Institute | Neurotransmitters and T. gondii
https://www.stanleyresearch.org/patient-and-provider-resources/toxoplasmosis-schizophrenia-research/neurotransmitters-and-t-gondii/
Jaroslav Flegr and his colleagues in Prague have studied the effects of T. gondii infection on the behavior of mice. […] In other publications, Flegr et al. have speculated that dopamine is the missing link between schizophrenia and toxoplasmosis, specifically suggesting that dopamine is increased by activated cytokines (e.g., IL2) as a consequence of infection. […] In addition to affecting dopamine, it is now clear that T. gondii may also affect the GABA and glutamate neurotransmitter system. […] A previously cited study on the effects of T. gondii infections on juvenile and adult mice also reported that T. gondii affects not only dopamine and GABA, but glutamate, serotonin and norepinephrine as well. […] Studies in cell cultures have demonstrated that T. gondii can influence of transcription of endogenous retroviruses. […] A study reported that 3 strains of T. gondii (types I, II, and III) exerted significantly different effects on dopamine, glutamate, and serotonin as well as on 2 neuropeptides.
#72 Stanley Medical Research Institute | Neurotransmitters and T. gondii
https://www.stanleyresearch.org/patient-and-provider-resources/toxoplasmosis-schizophrenia-research/neurotransmitters-and-t-gondii/
Jaroslav Flegr and his colleagues in Prague have studied the effects of T. gondii infection on the behavior of mice. […] In other publications, Flegr et al. have speculated that dopamine is the missing link between schizophrenia and toxoplasmosis, specifically suggesting that dopamine is increased by activated cytokines (e.g., IL2) as a consequence of infection. […] In addition to affecting dopamine, it is now clear that T. gondii may also affect the GABA and glutamate neurotransmitter system. […] A previously cited study on the effects of T. gondii infections on juvenile and adult mice also reported that T. gondii affects not only dopamine and GABA, but glutamate, serotonin and norepinephrine as well. […] Studies in cell cultures have demonstrated that T. gondii can influence of transcription of endogenous retroviruses. […] A study reported that 3 strains of T. gondii (types I, II, and III) exerted significantly different effects on dopamine, glutamate, and serotonin as well as on 2 neuropeptides.
#73 Toxoplasmosis and Neuropsychological Effects – Turkish Journal of Parasitology
https://www.turkiyeparazitolderg.org/articles/toxoplasmosis-and-neuropsychological-effects/doi/tpd.galenos.2020.6973
Toxoplasma gondii is an intracellular protozoan parasite. Approximately 30% of the global population is infected by T. gondii. In chronically infected individuals, the parasite resides in tissue cysts, especially in the brain. […] Until recent data, chronic latent toxoplasmosis has been viewed as a benign condition, however it has been proposed and supported mainly by experimental studies that such condition may have devastating effect on neuropsychological system via various introduced mechanisms. […] After entering the human body as in the form of tissue cysts, after passing beyond the stomach, the parasite excyst in the gut, cross the gut epithelium, continuing to increase in number. Once it is in the bloodstream, in its intracellular allocation, it can be transferred all across the body. Toxoplasma has a particular tropism for muscle and brain tissues where it may remain in a cystic form in a humans lifetime.
#74 Toxoplasmosis and Neuropsychological Effects – Turkish Journal of Parasitology
https://www.turkiyeparazitolderg.org/articles/toxoplasmosis-and-neuropsychological-effects/doi/tpd.galenos.2020.6973
Toxoplasma gondii is an intracellular protozoan parasite. Approximately 30% of the global population is infected by T. gondii. In chronically infected individuals, the parasite resides in tissue cysts, especially in the brain. […] Until recent data, chronic latent toxoplasmosis has been viewed as a benign condition, however it has been proposed and supported mainly by experimental studies that such condition may have devastating effect on neuropsychological system via various introduced mechanisms. […] After entering the human body as in the form of tissue cysts, after passing beyond the stomach, the parasite excyst in the gut, cross the gut epithelium, continuing to increase in number. Once it is in the bloodstream, in its intracellular allocation, it can be transferred all across the body. Toxoplasma has a particular tropism for muscle and brain tissues where it may remain in a cystic form in a humans lifetime.
#75 Toxoplasmosis and Neuropsychological Effects – Turkish Journal of Parasitology
https://www.turkiyeparazitolderg.org/articles/toxoplasmosis-and-neuropsychological-effects/doi/tpd.galenos.2020.6973
The plausible explanations for toxoplasmosis and schizophrenia are several. Toxoplasma spp. is a neurotropic parasite, with a special affinity to glial cells. The cysts consisting of bradyzoites can be found all over the brain. These cysts may lead to psychological changes by their anatomic location. […] Toxoplasma spp. adversely affects dopaminergic neurons via increased pro-inflammatory substances such as cytokines. Even in the later stages of the chronic disease, Toxoplasma spp. produce tyrosine hydroxylase and this enzyme causes a limitation in dopamine synthesis and dopamine deficiency may be associated with PD. […] Toxoplasma may exert its effect in the brain, which is mostly its primary target, in various ways. It affects neurons as well as astrocytes and microglial cells. Neurons are more vulnerable, because the latter cells may protect themselves due to their -to a certain level- capability to inhibit the parasite upon its arrival. In latent (chronic) infection with toxoplasma, parasites transform themselves into bradyzoite form and make brain tissue cysts.
#76 Toxoplasmosis and Neuropsychological Effects – Turkish Journal of Parasitology
https://www.turkiyeparazitolderg.org/articles/toxoplasmosis-and-neuropsychological-effects/doi/tpd.galenos.2020.6973
The plausible explanations for toxoplasmosis and schizophrenia are several. Toxoplasma spp. is a neurotropic parasite, with a special affinity to glial cells. The cysts consisting of bradyzoites can be found all over the brain. These cysts may lead to psychological changes by their anatomic location. […] Toxoplasma spp. adversely affects dopaminergic neurons via increased pro-inflammatory substances such as cytokines. Even in the later stages of the chronic disease, Toxoplasma spp. produce tyrosine hydroxylase and this enzyme causes a limitation in dopamine synthesis and dopamine deficiency may be associated with PD. […] Toxoplasma may exert its effect in the brain, which is mostly its primary target, in various ways. It affects neurons as well as astrocytes and microglial cells. Neurons are more vulnerable, because the latter cells may protect themselves due to their -to a certain level- capability to inhibit the parasite upon its arrival. In latent (chronic) infection with toxoplasma, parasites transform themselves into bradyzoite form and make brain tissue cysts.
#77 Toxoplasmosis and Neuropsychological Effects – Turkish Journal of Parasitology
https://www.turkiyeparazitolderg.org/articles/toxoplasmosis-and-neuropsychological-effects/doi/tpd.galenos.2020.6973
The underlying mechanism is not clear. However, there are 2 main proposed grounds for the relationship between toxoplasmosis and autism; one experimental study showed a clear relationship between toxoplasma infection and gluten antibody. […] There are case-control studies showing higher prevalence of seropositivity for toxoplasmosis in patients with cryptogenic epilepsy. […] Although the plausible mechanisms and meta-analysis stated above, there is a need for more clinical studies to yield a strong data between toxoplasmosis and epilepsy.
#78 Toxoplasmosis and Neuropsychological Effects – Turkish Journal of Parasitology
https://www.turkiyeparazitolderg.org/articles/toxoplasmosis-and-neuropsychological-effects/doi/tpd.galenos.2020.6973
The underlying mechanism is not clear. However, there are 2 main proposed grounds for the relationship between toxoplasmosis and autism; one experimental study showed a clear relationship between toxoplasma infection and gluten antibody. […] There are case-control studies showing higher prevalence of seropositivity for toxoplasmosis in patients with cryptogenic epilepsy. […] Although the plausible mechanisms and meta-analysis stated above, there is a need for more clinical studies to yield a strong data between toxoplasmosis and epilepsy.
#79 Toxoplasmosis: identification of a mechanism ensuring the immune surveillance of infection in the brain – Inserm Newsroom
https://presse.inserm.fr/en/toxoplasmose-identification-dun-mecanisme-assurant-la-surveillance-immunitaire-de-linfection-dans-le-cerveau/68699/
Toxoplasmosis is an infection caused by the parasite Toxoplasma gondii (T. gondii). In over one third of the human population, this parasite establishes a chronic infection of the brain which can have serious consequences in people with compromised immunity. […] The study, conducted by Inserm researcher Nicolas Blanchard and his team at the Toulouse Institute for Infectious and Inflammatory Diseases (Infinity, Universit Toulouse III Paul Sabatier, CNRS, Inserm), has shown that a category of immune cells known as resident CD8+ T cells plays a key role in detecting and neutralising the toxoplasmosis parasite in the brain. […] A better understanding of the immune mechanisms that control the parasite, particularly in the brain, could suggest new therapeutic strategies aimed at stimulating natural immunity to the parasite in order to better contain or even eliminate it.
#80 Azthena logo with the word Azthena
https://www.news-medical.net/news/20210624/Researchers-identify-key-role-of-enzyme-essential-for-invasion-of-the-toxoplasmosis-parasite.aspx
Scientists from the universities of Geneva and Zurich and the PSI have identified the structure and functions of RON13, an enzyme of the toxoplasmosis parasite that is essential for the infectious mechanism in humans. […] Understanding how the parasite manages to enter host cells offers new opportunities to develop more effective prevention and control strategies than those currently available. […] A team from the University of Geneva (UNIGE), in collaboration with the University of Zurich (UZH) and the Paul Scherrer Institute (PSI) in Villigen, Switzerland, have identified the key role of RON13, a protein of the parasite, which is essential for the invasion process. […] RON13 is a kinase located in a unique compartment of the parasite, an organelle containing proteins to be injected into the host. Without RON13, host cells infection is impossible.
#81 Scientists Uncover Process Enabling Toxoplasmosis Parasite to Survive Homelessness
https://medicine.iu.edu/news/2010/09/scientists-uncover-process-enabling-toxoplasmosis-parasite-to-survive-homelessness
Parasites such as Toxoplasma gondii invade host cells, replicate and then must exit to find new host cells to invade. […] The researchers found that the parasite triggers a stress response mechanism that alters protein production through phosphorylation of a factor called eIF2, which the Toxoplasma parasite uses to survive periods when it finds itself without a host cell. […] Toxoplasma does not like to be homeless, said William J. Sullivan Jr., Ph.D., associate professor of pharmacology and toxicology. Being deprived of the nutrients and shelter provided by the host cell is a serious stress on the parasite. Our research uncovered a critical pathway the parasite uses to survive the journey from one host cell to another. […] Based on earlier research, the group previously reported that the same response system is employed by the parasite when its host cell is stressed, which enables Toxoplasma to transform into a cyst surrounded by a protective barrier that can resist drugs and the bodys immune system. […] Our latest findings indicate that if we design new drugs that target this stress response pathway, these drugs may be effective against both acute and chronic Toxoplasma infection, says Dr. Sullivan.
#82 Exploring the potential of Toxoplasma gondii in drug development and as a delivery system | Experimental & Molecular Medicine
https://www.nature.com/articles/s12276-024-01165-7
Immune-mediated inflammatory diseases are various groups of conditions that result in immune system disorders and increased cancer risk. […] Several previous studies have demonstrated that Toxoplasma gondii manipulates the immune response by inhibiting or stimulating cytokines, suggesting the potential for controlling and maintaining a balanced immune system. Additionally, T. gondii also has the unique characteristic of being a so-called Trojan horse bacterium that can be used as a drug delivery system to treat regions that have been resistant to previous drug delivery therapies. […] T. gondii is a protozoan parasite that infects approximately one-third of the human population worldwide. T. gondii causes long-term chronic infection in the tissues of warm-blooded animals and humans and exists as a latent infection state primarily in the tissues of the central nervous system (CNS). Furthermore, T. gondii has developed self-preservation mechanisms to manipulate the immune systems of its hosts, such as by inducing an immune response or immune system evasion.
#83 Exploring the potential of Toxoplasma gondii in drug development and as a delivery system | Experimental & Molecular Medicine
https://www.nature.com/articles/s12276-024-01165-7
Interestingly, to resist the immune response, T. gondii has successfully evolved strategies to evade the host immune system and migrate to immune-privileged sites, such as the CNS. T. gondii prevents the host immune system from entering through multiple mechanisms, including transcriptional regulation and interference with cell signaling, resulting in the secretion of inflammatory cytokines, modulation of matrix metalloproteases (MMPs), production of microbicidal molecules and apoptosis. […] T. gondii infection leads to anti-inflammatory cytokine production through an altered host immune system by manipulating host gene transcription and regulating signaling pathways. […] T. gondii has unique characteristics for drug delivery. T. gondii can infiltrate the BBB using immune cells, as in Trojan horses. Drug delivery via T. gondii employs immune cells that are involved in various diseases, and this approach might be applied to various diseases for which existing drug delivery has been difficult, including cancer.
#84 CDC – DPDx – Toxoplasmosis
https://www.cdc.gov/dpdx/toxoplasmosis/index.html
Toxoplasma gondii is a protozoan parasite that infects most species of warm-blooded animals, including humans, and causes the disease toxoplasmosis. […] In the human host, the parasites form tissue cysts, most commonly in skeletal muscle, myocardium, brain, and eyes; these cysts may remain throughout the life of the host. […] Congenital toxoplasmosis results from an acute primary infection acquired by the mother during pregnancy. […] Ocular Toxoplasma infection, an important cause of retinochoroiditis in the United States, can be the result of congenital infection, or infection after birth. […] Toxoplasmosis in patients being treated with immunosuppressive drugs may be due to either newly acquired or reactivated latent infection. […] The diagnosis of toxoplasmosis may be documented by serologic testing, which is the routine method of diagnosis. […] Detection of parasite genetic material by PCR, especially in detecting congenital infections in utero and toxoplasmic encephalitis in people with HIV. […] The detection of Toxoplasma-specific antibodies is the primary diagnostic method to determine infection with Toxoplasma.
#85 CDC – DPDx – Toxoplasmosis
https://www.cdc.gov/dpdx/toxoplasmosis/index.html
Toxoplasma gondii is a protozoan parasite that infects most species of warm-blooded animals, including humans, and causes the disease toxoplasmosis. […] In the human host, the parasites form tissue cysts, most commonly in skeletal muscle, myocardium, brain, and eyes; these cysts may remain throughout the life of the host. […] Congenital toxoplasmosis results from an acute primary infection acquired by the mother during pregnancy. […] Ocular Toxoplasma infection, an important cause of retinochoroiditis in the United States, can be the result of congenital infection, or infection after birth. […] Toxoplasmosis in patients being treated with immunosuppressive drugs may be due to either newly acquired or reactivated latent infection. […] The diagnosis of toxoplasmosis may be documented by serologic testing, which is the routine method of diagnosis. […] Detection of parasite genetic material by PCR, especially in detecting congenital infections in utero and toxoplasmic encephalitis in people with HIV. […] The detection of Toxoplasma-specific antibodies is the primary diagnostic method to determine infection with Toxoplasma.
#86 CDC – DPDx – Toxoplasmosis
https://www.cdc.gov/dpdx/toxoplasmosis/index.html
Toxoplasma gondii is a protozoan parasite that infects most species of warm-blooded animals, including humans, and causes the disease toxoplasmosis. […] In the human host, the parasites form tissue cysts, most commonly in skeletal muscle, myocardium, brain, and eyes; these cysts may remain throughout the life of the host. […] Congenital toxoplasmosis results from an acute primary infection acquired by the mother during pregnancy. […] Ocular Toxoplasma infection, an important cause of retinochoroiditis in the United States, can be the result of congenital infection, or infection after birth. […] Toxoplasmosis in patients being treated with immunosuppressive drugs may be due to either newly acquired or reactivated latent infection. […] The diagnosis of toxoplasmosis may be documented by serologic testing, which is the routine method of diagnosis. […] Detection of parasite genetic material by PCR, especially in detecting congenital infections in utero and toxoplasmic encephalitis in people with HIV. […] The detection of Toxoplasma-specific antibodies is the primary diagnostic method to determine infection with Toxoplasma.
#87 toxoplasmosis etiology pathogenesis and treatment | PPT
https://www.slideshare.net/slideshow/toxoplasmosis-etiology-pathogenesis-and-treatment/266889491
oocyst shed in feaces develop into infective form in soil ingested by felines ingested by int.host repeat cycle sporozoites release form tachyzoites causes infection. […] Risk of foetal infection: 25% – I trimester; severity is high 65% – III trimester Chorioretinitis, strabismus, blindness, deafness, hydrocephalus, microcephaly, MR, epilepsy, cerebral calcification, glaucoma, pneumonitis, myocarditis, HSM etc. […] Avidity of IgG antibodies against T. gondii thus, is a useful marker to differentiate between recent and remote infection.
#88 Toxoplasmosis in Animals – Generalized Conditions – Merck Veterinary Manual
https://www.merckvetmanual.com/generalized-conditions/toxoplasmosis/toxoplasmosis-in-animals
Toxoplasmosis is an important zoonotic protozoal infection worldwide. […] Toxoplasmosis is diagnosed by biologic, serologic, or histologic methods; or some combination of these. […] The tachyzoite is the stage responsible for tissue damage in toxoplasmosis; therefore, clinical signs depend on the affected tissue, the number of tachyzoites released, and the ability of the host immune system to limit replication and transmission. […] Tachyzoites infect tissues throughout the body and replicate intracellularly until the cells burst, causing tissue necrosis. […] Tachyzoites may also be transmitted to the fetus, causing necrosis in multiple organs. […] Toxoplasmosis is also a concern for pregnant women because tachyzoites can migrate transplacentally and cause neurologic disorders in the fetus.