Materiały źródłowe

• #1 Giardiasis – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK513239/

  Giardiasis is caused by the protozoan Giardia duodenalis, also known as G lamblia and G intestinalis. Infected animals excrete cysts into freshwater, which remain infective and viable for weeks to months. There are 7 distinct genetic assemblages (A to F), but only genotypes A and B have been found to infect humans. […] Human infection occurs through ingesting cysts via contaminated water or direct person-to-person contact, with transmission heavily influenced by inadequate hygiene and sanitation practices. Daycares have emerged as epicenters of infection due to insufficient handwashing protocols, especially during diaper handling and changing. […] The exact mechanism behind the symptoms of giardiasis remains unclear. Trophozoites possess a ventral disk, which they use to attach themselves to the intestinal epithelium. Researchers theorize that these protozoa disrupt small intestine epithelial cell junctions and brush border enzymes. Consequently, infected patients might display altered gastrointestinal motility. The protozoa release thiol proteinases and lectins that have a cytopathic effect. The combination of these effects increases permeability and impairs the processing of saccharides.

• #2 Giardiasis: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/176718-overview

  Infection with Giardia intestinalis most often results from fecal-oral transmission or ingestion of contaminated water. Contaminated food is a less common etiology. Person-to-person spread is common, with 30% of family members with infected children themselves becoming infected. […] The mechanisms by which Giardia causes diarrhea and intestinal malabsorption are probably multifactorial and not yet fully elucidated. Postulated mechanisms include damage to the endothelial brush border, enterotoxins, immunologic reactions, and altered gut motility and fluid hypersecretion via increased adenylate cyclase activity. […] Adhesion of trophozoites to the epithelium has been demonstrated to cause increased epithelial permeability. Giardia-induced loss of intestinal brush border surface area, villus flattening, inhibition of disaccharidase activities, and eventual overgrowth of enteric bacterial flora appear to be involved in the pathophysiology of giardiasis but have yet to be causatively linked to the disease’s clinical manifestations.

• #2 Giardiasis: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/176718-overview

  Enterocytic injury is mediated by activated host T lymphocytes. Pathophysiological activation of lymphocytes is secondary to Giardia-induced disruption of epithelial tight junctions, which, in turn, increases intestinal permeability. Loss of epithelial barrier function is a result of Giardia-induced enterocyte apoptosis. […] Giardia can also prevent the formation of nitric oxide, a compound known to inhibit giardial growth, by consuming local arginine, which effectively removes the substrate needed by enterocytes to produce nitric oxide. This mechanism may contribute to Giardia-induced enterocyte apoptosis, because arginine starvation in these cells is known to result in programmed cell death. […] G intestinalis is genetically heterogeneous with eight genetically distinct genotypes or assemblages, designated A-H; assemblages A and B can infect humans. Genotypes vary within group A and B, which could explain why the role of animals in the epidemiology of human infection remains poorly understood. Some strains appear more biologically suitable than other strains. This feature is potentially important in giardiasis pathogenesis. Genotypically diverse isolates of Giardia species may vary in their ability to produce morphologic changes in the small intestine epithelium and to impair fluid, electrolyte, and solute transport.

• #3 CDC – DPDx – Giardiasis

  https://www.cdc.gov/dpdx/giardiasis/index.html

  Giardia duodenalis is a protozoan flagellate (Diplomonadida). […] Cysts are resistant forms and are responsible for transmission of giardiasis. Both cysts and trophozoites can be found in the feces (diagnostic stages). […] Infection occurs by the ingestion of cysts in contaminated water, food, or by the fecal-oral route (hands or fomites). […] In the small intestine, excystation releases trophozoites (each cyst produces two trophozoites). […] Trophozoites multiply by longitudinal binary fission, remaining in the lumen of the proximal small bowel where they can be free or attached to the mucosa by a ventral sucking disk. […] Encystation occurs as the parasites transit toward the colon. […] Because the cysts are infectious when passed in the stool or shortly afterward, person-to-person transmission is possible.

• #4 Giardiasis – Knowledge @ AMBOSS

  https://www.amboss.com/us/knowledge/giardiasis/

  Giardia have 2 stages in the life cycle. […] Ingestion of cysts excystation and conversion to trophozoite form rapid multiplication, adhesion to intestinal walls encystation in large bowel excretion of cysts possible reinfection. […] Although several theories exist, it is commonly suspected that infection with Giardia leads to impaired function and structure of intestinal tissue, resulting in malabsorption and diarrhea. […] IgA deficiencies (e.g., selective IgA deficiency, X-linked agammaglobulinemia, common variable immunodeficiency) increases susceptibility to giardiasis because of the disruption of gastrointestinal protective barrier.

• #5

  https://link.springer.com/article/10.1007/s40588-015-0026-y

  Flagellar motility may play a mechanical role in the initial opening of the cyst, in addition to contractile or other MT-mediated forces, and is also required for positioning of the trophozoite prior to attachment. […] The ventral disc, a spiral microtubule array, mediates trophozoite attachment via an as-yet-unknown mechanism. […] Microtubule dynamics can be influenced by microtubule-associated proteins (MAPs), such as EB1, and microtubule-based molecular machines, such as kinesins. […] While microtubule-based mechanisms of flagellar motility and mitosis are similar to those in model eukaryotic experimental systems, Giardia-specific cytoskeletal mechanisms, including ventral disc-mediated surface attachment and excystation/encystation, are less understood. […] The ventral disc is a large microtubule-based structure that is unique to Giardia and facilitates the attachment of the parasite to surfaces.

• #5

  https://link.springer.com/article/10.1007/s40588-015-0026-y

  Giardia lamblia is a flagellated parasite of the gut and causes significant morbidity worldwide. […] Giardia’s conserved and unique cytoskeletal features, such as its eight flagella and ventral disc, are required for host colonization by facilitating motility, attachment, and cell division. […] At the cellular level, Giardia colonization of the host is known to result in villus shortening, enterocyte apoptosis, and intestinal barrier dysfunction. […] The Giardia genome does encode over 300 variant surface protein (VSP) genes, and antigen switching of (VSPs) likely contributes to the evasion of immune screening. […] Giardia’s complex microtubule (MT) cytoskeleton, including its ventral disc and flagella, is of critical importance throughout both stages of its life cycle.

• #6 Novel Structural Components of the Ventral Disc and Lateral Crest in Giardia intestinalis | PLOS Neglected Tropical Diseases

  https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0001442

  The ventral disc is a highly ordered and complex spiral microtubule array (150400 nm thick) with elaborated structures that protrude dorsally into the cell body. […] The composition and function of the trilaminar microribbons, microribbon-connecting crossbridges, and MT-associated sidearm structures are unknown. […] The lateral crest is a repetitive structure surrounding the ventral disc that is comprised of a network of fibers of unknown composition and is putatively contractile. […] We have recently shown by TIRFM that the lateral crest contacts the surface, forming a critical seal when trophozoites attach. […] The novel DAPs (seven ankyrin repeat proteins, two Nek pseudokinases and one novel protein) that localize to the disc perimeter likely comprise the lateral crest structure that surrounds the ventral disc.

• #7 The Molecular Pathogenesis of Giardiasis

  https://www.periodicos.capes.gov.br/index.php/acervo/buscador.html?task=detalhes&id=W2106326883

  In human giardiasis, even when villous architecture appears normal by light microscopy, ultrastructural changes such as shortening and disruption of microvilli are present. […] The mechanisms by which Giardia causes diarrhoea and intestinal malabsorption remain controversial. […] Giardia trophozoites attach to the epithelium and have been shown by electromicroscopy to disrupt and distort microvilli at the site where the ventral disc interfaces with the microvillus membrane. […] There is some evidence to suggest that Giardia itself produces, and possibly releases, cytopathic substances into the intestinal lumen. […] Giardia does, however, contain a number of thiol proteinases which might attack surface glycoproteins and disrupt microvillus membrane integrity. […] Whatever the mechanism by which Giardia damages villus epithelial cells and presumably produces increased epithelial cell loss, there would appear to be a predictable crypt cell response with an increase in crypt depth and crypt cell proliferation.

• #7 The Molecular Pathogenesis of Giardiasis

  https://www.periodicos.capes.gov.br/index.php/acervo/buscador.html?task=detalhes&id=W2106326883

  Finally, Giardia appears to be able to influence a number of important physiological events within the intestinal lumen and to interfere with the digestive process as well as the absorptive function of the small intestinal epithelium. […] Infection is initiated by ingestion of Giardia cysts, generally through contaminated water or food; direct person-to-person transfer does occur. […] Colonisation of the small intestine is an essential component of Giardia’s life cycle and a sine qua non for the production of diarrhoeal disease. […] Giardia attaches intimately to the intestinal epithelium and to a variety of other inert substrates such as glass and plastic. […] The ventral disc is thought to be the primary organelle of attachment. […] It has also been suggested that flagella activity causes low pressure under the ventral disc due to fluid fluxes around the ventral and marginal grooves.

• #7 The Molecular Pathogenesis of Giardiasis

  https://www.periodicos.capes.gov.br/index.php/acervo/buscador.html?task=detalhes&id=W2106326883

  The presence of contractile proteins in the peripheral regions of the ventral disc suggests that they participate in attachment. […] Giardia trophozoites divide by binary fission. […] Encystation is essential for the parasite to complete its life cycle and survive in the external environment or be carried by other hosts such as domestic and wild animals. […] Giardia is usually found in close proximity to the apical surface of the enterocyte, often penetrating deep into the intestinal crypts. […] One of the difficulties in explaining the pathology and pathophysiology of giardiasis relates to the extensive spectrum of disease expression, which ranges from symptom-free carriage of the organism to chronic diarrhoea and malabsorption. […] In human giardiasis, there may be no light microscopic abnormalities in the proximal small intestine; in hospital-based series, probably 20-25% of patients fall into this category.

• #7 The Molecular Pathogenesis of Giardiasis

  https://www.periodicos.capes.gov.br/index.php/acervo/buscador.html?task=detalhes&id=W2106326883

  Giardia intestinalis (formerly known as Giardia lamblia) is the most common human protozoan pathogen. […] There is no satisfactory explanation for the diverse clinical spectrum seen in giardiasis, and as yet no virulence factors have been identified. […] The failure to identify the parasite determinants responsible for the production of intestinal injury, diarrhoea, and malabsorption makes it impossible to provide a simple explanation for the molecular pathogenesis of giardiasis. […] However, there have been some important steps forward in understanding the disease mechanisms, particularly the concept of genetic diversity, within the Giardia genus. […] This observation alone could be of great assistance in the isolation of specific virulence factors in the future. […] For more than two decades there has been evidence that mucosal immune responses may be involved in the development of the enteropathy associated with giardiasis.

• #7 The Molecular Pathogenesis of Giardiasis

  https://www.periodicos.capes.gov.br/index.php/acervo/buscador.html?task=detalhes&id=W2106326883

  Work in our laboratory has shown, however, that Giardia can directly stimulate the enzyme ornithine decarboxylase (ODC), a rate-limiting enzyme in polyamine synthesis and cell proliferation, in Caco-2 cells in vitro and in neonatal rat small intestine in vivo. […] From the foregoing discussion it is clear that no single virulence factor or unifying mechanism explains the pathogenesis of giardiasis. […] However, preliminary factors that might impair digestive processes could well be part of a malabsorptive consortium, but it seems unlikely that they alone can explain the diarrhoea and malabsorption associated with this infection. […] Thus, we are left with the somewhat unsatisfactory situation of having to accept, in our present state of ignorance, a multifactorial and possibly a multistep process of pathogenesis.

• #8 Giardia lamblia: Morphology, life cycle, pathogenesis, clinical manifestation, lab diagnosis and treatment – Online Biology Notes

  https://www.onlinebiologynotes.com/giardia-lamblia-morphology-life-cycle-pathogenesis-clinical-manifestation-lab-diagnosis-and-treatment/

  Giardia is intestinal parasite and it is non-invasive. […] Once excystation occurs, trophozoites are releases and they uses their flagella to swim to the microvilli covered surface of duodenum and jejunum where they attach to the enterocytes using their adhesive disc. […] Lectins present on the surface of Giardia binds to receptor present on surface of enterocytes. This attachment process damage microvilli, which interfere with nutrition absorption by villi. […] Rapid multiplication of trophozoites eventually creates a physical barriers between the enterocytes and intestinal lumen, further interfering with nutrition absorption. This process leads to enterocytes damage, villi atropy, crypt hyperplasia, intestinal hyperpermeability and brush boarder damage that causes a reduction in disaccharide enzyme secretion.

• #8 Giardia lamblia: Morphology, life cycle, pathogenesis, clinical manifestation, lab diagnosis and treatment – Online Biology Notes

  https://www.onlinebiologynotes.com/giardia-lamblia-morphology-life-cycle-pathogenesis-clinical-manifestation-lab-diagnosis-and-treatment/

  Lectins and othere cytopathic substance secreted by parasite also causes indirect damage to intestinal epithelium. […] Trophozoites do not invade or penetrate surrounding tissue or enter blood stream. So, infection is generally restricted to intestinal lumen. […] Giardiasis results in decreased jejunal electrolyte water and glucose absorptiom, and damages to intestinal epithelium leads to malabsorption of electrolyte and fluids, resulting in osmotic diarrhea known as giardiasis.

• #9 The domed architecture of Giardia’s ventral disc is necessary for attachment and host pathogenesis | bioRxiv

  https://www.biorxiv.org/content/10.1101/2023.07.02.547441v1

  After ingestion of dormant cysts, the widespread protozoan parasite Giardia lamblia colonizes the host gastrointestinal tract via direct and reversible attachment using a novel microtubule organelle, the ventral disc. […] Extracellular attachment to the host allows the parasite to resist peristaltic flow, facilitates colonization and is proposed to cause damage to the microvilli of host enterocytes as well as disrupt host barrier integrity. […] Overall, this work provides direct evidence of the role of MBP in creating the domed disc, as well as the first direct evidence that parasite attachment is necessary for host pathology, specifically epithelial barrier breakdown.

• #10 Giardiasis: Characteristics, Pathogenesis and New Insights About Treatment | Bentham Science Publishers

  https://www.benthamdirect.com/content/journals/ctmc/10.2174/1568026618666181002095314

  Giardia intestinalis infection causes enterocytes damage and loss of brush border of the epithelial cells of the intestine that leads to shortening of microvilli and altered epithelial barrier function. […] The main consequence of Giardia colonization is nutrients malabsorption.

• #11 The Pathogenesis of Giardia Intestinalis

  https://ouci.dntb.gov.ua/en/works/4kRR3267/

  Giardia intestinalis infection leads to intestinal cell damage and loss of the brush border of the intestinal epithelium, resulting in shortened microvilli and impaired epithelial barrier function. […] In recent years, its pathogenesis, including structural proteins and excretion of Giardia intestinalis, surface antigen variants, and the role of Giardia intestinalis in the small intestine, has been extensively studied. […] This article discusses this issue and lists the risks of Giardia intestinalis to the human intestine and the various diseases it can cause.

• #12

  https://link.springer.com/article/10.1007/s40475-015-0049-8

  Overall, Giardia-induced diffuse shortening of brush border microvilli causes small intestinal malabsorption due to impaired absorption of water, glucose, and electrolytes. […] Recent findings indicate that the pathogenic effects of Giardia may be further compounded by degradation of local mucins by the parasite, which may in turn contribute to the translocation of commensal bacteria through the epithelium. […] While at least some of the pathogenic effects of Giardia are isolate-dependent, the identification of a Giardia enterotoxin has remained elusive. […] Cathepsin-like cysteine proteases are key components of the pathogenesis of several protozoan parasitic disorders, and the Giardia genome contains genes for 23 of those proteases. […] Recent findings also suggest a role for these proteases in the disruption of enterocytic cytoskeletal villin.

• #12

  https://link.springer.com/article/10.1007/s40475-015-0049-8

  Impaired enterocyte cell cycle and proliferation, via the consumption of host arginine by the parasite, have also been suggested to contribute to pathogenesis. […] The reduction in intestinal barrier function induced by giardiasis implicates disruptions of F-actin, zonula occludens 1 (ZO-1), claudin-1 and claudin-4, occludin, and -actinin, the latter being a component of the actomyosin ring that regulates paracellular flow. […] Loss of epithelial barrier integrity is mediated by activation of epithelial myosin light chain kinase. […] Disruptions of epithelial tight junctional proteins by Giardia are caspase-3-dependent, similarly to other enteric disorders. […] However, recent findings also point to a direct role for cysteine proteases released by the parasite in the proteolytic disruption of epithelial villin, an important constituent of brush border microvilli.

• #12

  https://link.springer.com/article/10.1007/s40475-015-0049-8

  Giardiasis occurs in the absence of invasion of the intestinal tissues by the trophozoites and in the absence of any overt inflammatory cell infiltration, with the exception of a modest increase in intraepithelial lymphocytes and mast cells. […] Recent observations have demonstrated that this effect may be due to a direct immuno-modulating effect of the parasite via its cathepsin B cysteine protease which cleaves pro-inflammatory CXCL8. […] No known toxin has yet been directly implicated in the pathophysiology of giardiasis. […] The pathophysiology of acute diarrhea in giardiasis implicates increased rates of enterocyte apoptosis, a disruption of the intestinal barrier function, activation of host lymphocytes, CD8+ lymphocyte-mediated shortening of brush border microvilli with or without coinciding villous atrophy, disaccharidase deficiencies, small intestinal malabsorption, anion hypersecretion, and increased intestinal transit rates.

• #13 Giardiasis – Wikipedia

  https://en.wikipedia.org/wiki/Giardiasis

  The attachment of trophozoites causes villous flattening and inhibition of enzymes that break down disaccharide sugars in the intestines. Ultimately, the community of microorganisms that lives in the intestine may overgrow and may be the cause of further symptoms, though this idea has not been fully investigated. The alteration of the villi leads to an inability of nutrient and water absorption from the intestine, resulting in diarrhoea, one of the predominant symptoms. […] The species Giardia intestinalis uses enzymes that break down proteins to attack the villi of the brush border and appears to increase crypt cell proliferation and crypt length of crypt cells existing on the sides of the villi. On an immunological level, activated host T lymphocytes attack endothelial cells that have been injured to remove the cell. This occurs after the disruption of proteins that connect brush border endothelial cells to one another. The result is increased intestinal permeability.

• #13 Giardiasis – Wikipedia

  https://en.wikipedia.org/wiki/Giardiasis

  There appears to be a further increase in programmed enterocyte cell death by Giardia intestinalis, which further damages the intestinal barrier and increases permeability. There is significant upregulation of the programmed cell death cascade by the parasite, and substantial downregulation of the anti-apoptotic protein Bcl-2 and upregulation of the proapoptotic protein Bax. These connections suggest a role of caspase-dependent apoptosis in the pathogenesis of giardiasis. […] Giardia protects its growth by reducing the formation of the gas nitric oxide by consuming all local arginine, which is the amino acid necessary to make nitric oxide. Arginine starvation is known to be a cause of programmed cell death, and local removal is a strong apoptotic agent.

• #14 BugBitten Giardiasis from Proteomics to Pathogenesis

  https://blogs.biomedcentral.com/bugbitten/2018/03/23/giardiasis-from-proteomics-to-pathogenesis/

  To win the fight against parasitic diahorreal disease, the molecular detail of pathogenesis must be understood. […] The established narrative of pathogenesis is trophozoite attachment to the duodenal epithelium via a ventral disc which sometimes (but not always) causes villus atrophication by apoptosis (programmed cell death) of surrounding cells, initiating inflammation and disrupting intestinal barrier function. […] Localized damage cannot be the sole cause of the profound diarrhoea that can affect the intestinal absorption over a much wider area of the digestive tract than the site of colonization suggesting a role for soluble, secreted, virulence factors. […] Most of the proteins highlighted as secreted and up-regulated by trophozoites belong to three major group of proteins: Giardia tenascins, cathepsin B precursors (GCATBs) and high cysteine membrane proteins (HCMPs).

• #14 BugBitten Giardiasis from Proteomics to Pathogenesis

  https://blogs.biomedcentral.com/bugbitten/2018/03/23/giardiasis-from-proteomics-to-pathogenesis/

  A novel mechanism of early pathogenesis has been proposed: Pyridoxamine 5phosphate oxidase (PNPO), secreted by Giardia, produces a reducing environment favouring the growth of Giardia trophozoites. […] Giardia extracellular nuclease degrades the outer layer of the intestinal mucus granting better access to the mucus layer to GCATBs. […] Further degradation of the protective intestinal mucus barrier may be caused by GCATBs as well as subsequent disruption of the intestinal intracellular junctions. […] Tenascins are likely to be responsible for reducing adhesion between epithelial cells and thereby maintaining intestinal cell separation. […] Giardia mediated dismantling of the barriers provided by the mucosal membranes and modulation of the environment leaves the intestinal epithelia prone to secondary infections by opportunist microbes residing in the intestinal lumen and sensitive to irritation by allergens in foodstuffs.

• #15 Giardiasis in Animals – Digestive System – Merck Veterinary Manual

  https://www.merckvetmanual.com/digestive-system/giardiasis-giardia/giardiasis-in-animals

  Giardiasis infections cause an increase in epithelial permeability, increased numbers of intraepithelial lymphocytes, and activation of T lymphocytes. […] Trophozoite toxins and T-cell activation initiate a diffuse shortening of brush border microvilli and decreased activity of the small-intestinal brush border enzymes, especially lipase, some proteases, and disaccharidases. […] The diffuse microvillus shortening leads to a decrease in overall absorptive area in the small intestine and thus an impaired intake of water, electrolytes, and nutrients. […] In addition, the proteins secreted by Giardia trophozoites contribute to degrading the intestinal mucous barriers and disrupting the intestinal intracellular junctions. […] The combined effect of decreased resorption, brush-border enzyme deficiencies, and a lack of integrity between cells of the intestine results in dysregulation of the absorption and barrier functions of the intestinal epithelium, resulting in malabsorptive diarrhea.

• #15 Giardiasis in Animals – Digestive System – Merck Veterinary Manual

  https://www.merckvetmanual.com/digestive-system/giardiasis-giardia/giardiasis-in-animals

  The reduced activity of lipase and the increased production of mucin by goblet cells may explain the steatorrhea and mucous diarrhea that has frequently been described in symptomatic giardiasis. […] Giardia infection has, in some circumstances, been associated with a lower likelihood of viral and bacterial infection, possibly via immunologic pathways.

• #16 Giardiasis pathophysiology – wikidoc

  https://www.wikidoc.org/index.php/Giardiasis_pathophysiology

  Giardia is usually transmitted via the fecal-oral route through personal contact and contaminated water and food. […] The mechanism of pathogenesis of Giardia is thought to include increased pro-apoptotic processes, subsequent loss of intestinal epithelial barrier, hypersecretion of electrolytes, and increased exposure to luminal antigens to subepithelial host immune cells. […] It is thought that Giardia induces caspase-mediated enterocytic apoptosis and results in the impairment of cellular tight junction integrity. […] Enterocyte apoptosis results in the loss of the intestinal epithelial barrier and subsequent increased permeability. […] The increased susceptibility of subepithelial immune activation, particularly CD8+ T-cells, results in local inflammation and the retraction of the microvilli of the small intestine (shortening of the intestinal brush border).

• #16 Giardiasis pathophysiology – wikidoc

  https://www.wikidoc.org/index.php/Giardiasis_pathophysiology

  Despite the absence of villus atrophy, giardiasis-mediated immune cell activation results in intestinal malabsorption through the process of diffuse microvilli shortening, whereby microvilli are unable to absorb nutrients in the intestinal lumen. […] In addition, electrolytes are hypersecreted (e.g. chloride hypersecretion), resulting in fluid accumulation in the intestinal lumen and development of clinical manifestations (i.e. watery diarrhea).

• #17

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8404698/

  The role of excretory secretory products (ESPs), most notably the cysteine proteases, has received substantial attention over the last decade. Although serine proteases are also present in the ESP, the major portion of the protease activity is from the cysteine proteases. It may be that the primary role of these proteases is to control encystation and excystation, but they also play roles in the interaction between the trophozoite and the host intestinal epithelium. […] Trophozoites interfere with the intestinal tight junction by a number of mechanisms that include the cysteine proteases. A study of the effect of CP2 (called giardipain 1 in this study) on an intestinal epithelial cell line (IEC-6) monolayer demonstrated damage to the cell junctions that was prevented by the protease inhibitor E-64. In addition, CP2 induces apoptosis and damages the villi by its interaction with villin.

• #17

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8404698/

  The intestinal mucus layer is a key component of innate defense against pathogens and, as such, it is notable that the cysteine proteases have a complex effect on the mucus. MUC2 (human mucus protein) is degraded in vitro, and MUC2 gene expression in goblet-like cells is increased, leading to the hypothesis that the Giardia cysteine proteases may deplete the normal intestinal mucus reserve.

• #17

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8404698/

  Giardia duodenalis is a noninvasive pathogen of the small intestine and produces a wide range of clinical presentations, including chronic diarrhea with weight loss, postinfectious complications of irritable bowel and chronic fatigue, growth stunting, and asymptomatic infections. […] Recent in-depth reviews of these advances are also available. The trophozoites adhere tightly to the small intestinal mucosa, leaving a detectable imprint when they detach from the intestinal epithelium, so the possibility of direct pathogenesis from the mechanical attachment has been raised. However, there is currently no evidence to support this possibility. Rather, current data suggest that a combination of secreted proteases and other Giardia factors, the host immune response, and the interaction of these factors with the intestinal microbiota contribute to the various manifestations.

• #18 Giardia duodenalis: New Research Developments in Pathophysiology, Pathogenesis, and Virulence Factors

  https://ucalgary.scholaris.ca/items/118da49d-0d2c-4326-95df-1884167c0b59

  Giardiasis occurs in the absence of invasion of the intestinal tissues by the trophozoites and in the absence of any overt inflammatory cell infiltration, with the exception of a modest increase in intraepithelial lymphocytes and mast cells. […] Recent observations have demonstrated that this effect may be due to a direct immuno-modulating effect of the parasite via its cathepsin B cysteine protease which cleaves pro-inflammatory CXCL8. […] No known toxin has yet been directly implicated in the pathophysiology of giardiasis. […] Findings from ongoing research indicate that the post-infectious effects of giardiasis may be due to microbiota dysbiosis induced by the parasite during the acute phase of infection.

• #19 The Influence of the Protozoan Giardia lamblia on the Modulation of the Immune System and Alterations in Host Glucose and Lipid Metabolism

  https://www.mdpi.com/1422-0067/25/16/8627

  G. lamblia secretes various proteases, including cathepsin B-like cysteine proteases and giardipain-1, which degrade host proteins, disrupt the epithelial barrier, induce apoptosis in intestinal epithelial cells, and modulate host immune responses. […] Studies conducted on in vivo and in vitro models have shown that G. lamblia causes disturbances in the absorption of glucose, sodium, and water, and reduces disaccharidase activity by reducing the absorptive surface area of the epithelium. […] G. lamblia affects intestinal motility by limiting the movements of intestinal villi and muscle contractions, disrupting the coordination of villi movements and disturbing the balance of gut microbiota. […] The combined effects of Giardia’s virulence factors on intestinal motility and microbiota composition interact to induce intestinal inflammation and disturb the absorption of lipids, carbohydrates, and other essential nutrients.

• #20 High-fat diet increases the severity of Giardia infection in association with low-grade inflammation and gut microbiota dysbiosis | Scientific Reports

  https://www.nature.com/articles/s41598-021-98262-8

  Disruptions of the mucus lining combined with goblet cell hyperplasia have been recently identified as pathogenic markers in giardiasis. Findings from the present study reveal a key role for altered Muc2 and Atoh1 gene expression in this phenomenon. Indeed, increased goblet cell counts in infected animals was exacerbated by the HF diet, in association with elevated Muc2 and Atoh1 gene expression. […] The gut microbiota has been shown to directly determine hosts susceptibility and/or resistance to colonization and persistence of G. duodenalis in mice. Giardia causes dysbiosis, disrupts the microbiota biofilm overlaying the mucosa, and promotes the release of pathobionts from commensal communities, in turn leading to functional abnormalities in the gut. […] The results suggest that Giardia-induced alterations in gastrointestinal motility and stool water contents are exacerbated by a HF diet.

• #21 SciELO Brasil – Immunopathology of giardiasis: the role of lymphocytes in intestinal epithelial injury and malfunction Immunopathology of giardiasis: the role of lymphocytes in intestinal epithelial injury and malfunction

  https://www.scielo.br/j/mioc/a/76SXchVTjgLchmvYkBHfLnC/

  T lymphocyte-mediated pathogenesis is common to a variety of enteropathies, including giardiasis, cryptosporidiosis, bacterial enteritis, celiac’s disease, food anaphylaxis, and Crohn’s disease. […] In giardiasis as well as in these other disorders, a diffuse loss of microvillous brush border, combined or not with villus atrophy, is responsible for disaccharidase insufficiencies and malabsorption of electrolytes, nutrients, and water, which ultimately cause diarrheal symptoms. […] Recent studies using models of giardiasis have shed new light on the immune regulation of these abnormalities. […] Indeed, experiments using an athymic mouse model of infection have found that these epithelial injuries were T cell-dependent. […] Findings from further research indicate that that the loss of brush border surface area, reduced disaccharidase activities, and increase crypt-villus ratios are mediated by CD8+ T cells, whereas both CD8+ and CD4+ small mesenteric lymph node T cells regulate the influx of intra-epithelial lymphocytes.

• #21 SciELO Brasil – Immunopathology of giardiasis: the role of lymphocytes in intestinal epithelial injury and malfunction Immunopathology of giardiasis: the role of lymphocytes in intestinal epithelial injury and malfunction

  https://www.scielo.br/j/mioc/a/76SXchVTjgLchmvYkBHfLnC/

  Future investigations need to characterize the CD8+ T cell signaling cascades that ultimately lead to epithelial injury and malfunction in giardiasis and other malabsorptive disorders of the intestine. […] Together these observations imply a protective function for T-cells in giardiasis, as well as a role for T-cells in the pathogenesis of intestinal villus injury. […] Recent findings indicate that in giardiasis this brush border injury and malfunction are mediated by CD8+ T lymphocytes. […] Data published to date support a role for CD4+ T lymphocytes in protective immunity, while CD8+ cells are implicated in pathophysiology. […] The findings from studies in giardiasis demonstrating that CD8+ lymphocytes are implicated in brush border injury and malfunction are consistent with this hypothesis.

• #22 Immunological aspects of Giardia infections | Parasite

  https://www.parasite-journal.org/articles/parasite/full_html/2014/01/parasite140090/parasite140090.html

  Immunodeficiency, particularly antibody deficiency, predisposes to increased intensity and persistence of Giardia infections. Giardia-infected immunocompetent hosts produce serum and intestinal antibodies against Giardia trophozoites. The number of Giardia muris trophozoites, in mice with G. muris infection, is reduced by intra-duodenal administration of anti-G. muris antibody. Giardia intestinalis antigens that are recognised by human anti-trophozoite antibodies include variable (variant-specific) and invariant proteins. Nitric oxide (NO) appears to contribute to host clearance of Giardia trophozoites. Arginine is a precursor of NO and is metabolised by Giardia trophozoites, possibly reducing its availability for generation of NO by the host. Work with mice suggests that T lymphocytes and interleukin-6 (IL-6) contribute to clearance of Giardia infection via mechanisms independent of antibodies.

• #22 Immunological aspects of Giardia infections | Parasite

  https://www.parasite-journal.org/articles/parasite/full_html/2014/01/parasite140090/parasite140090.html

  Giardia infections are increased in intensity and/or duration in human or non-human mammalian hosts with various forms of immunodeficiency, in comparison with their immunocompetent counterparts. This situation indicates that host immunological responses limit the intensity and/or duration of these infections. The extant literature suggests that impaired production of anti-Giardia antibodies is the main reason why immunodeficiency states predispose to severe/prolonged Giardia infections. […] A plausible mechanism for presumed antibody-mediated clearance of Giardia infections would involve prevention (by antibodies) of trophozoite attachment to the host intestinal epithelium followed by peristaltic expulsion of these organisms from the intestine. […] Experimental work with mice has suggested that T lymphocytes can contribute directly (i.e., in the absence of antibodies) to clearance of infection with a clone of G. intestinalis (GS/M-H7). The mechanism(s) involved in this putative T-cell-mediated clearance of Giardia infection does not appear to be known.

• #22 Immunological aspects of Giardia infections | Parasite

  https://www.parasite-journal.org/articles/parasite/full_html/2014/01/parasite140090/parasite140090.html

  Studies of Giardia infections in rodents have implicated interleukin-6 (IL-6) in anti-Giardia immunity. IL-6-deficient mice have a diminished ability to clear infection caused by G. intestinalis. The mice studied in the pertinent experiments were able to produce intestinal anti-trophozoite IgA; the findings suggest that IL-6 contributes to clearance of Giardia infection in mice (albeit by an unknown mechanism that appears not to involve IgA). Recent work has identified dendritic cells (of bone marrow origin) as a source of IL-6 that promotes clearance of G. intestinalis infection in mice. […] There is evidence that intestinal nitric oxide (NO) contributes to host clearance of Giardia trophozoites. In view of the fact that arginine is a substrate for generation of NO, it is interesting that Giardia trophozoites appear to compete with the host for arginine. Giardia trophozoites are able to metabolise arginine. Uptake and metabolism of arginine by Giardia trophozoites has implications for host nutrition (reducing the proportion of dietary arginine available for absorption by the host), as well as for trophozoite survival via reduced availability of arginine for host NO production.

• #23 Enteric Protozoa: Giardia and Cryptosporidium – Canada.ca

  https://www.canada.ca/en/health-canada/services/environmental-workplace-health/reports-publications/water-quality/enteric-protozoa-giardia-cryptosporidium.html

  Giardia and Cryptosporidium are common parasites in the gut of humans and other mammals. They, like enteric bacteria and viruses, can be found in water following direct or indirect contamination by the faeces of humans and other animals. These microorganisms can be transmitted via drinking water and have been associated with several waterborne outbreaks in North America and elsewhere. The ability of this group of microorganisms to produce (oo)cysts that are extremely resistant to environmental stresses and commonly used chlorine-based disinfectants has facilitated their ability to spread and cause illness. […] The specific mechanisms by which Giardia causes illness are not well understood, and no specific virulence factors have been identified. Some suggest that Giardia causes mechanical irritation or mucosal injury by attaching to the brush border of the intestinal tract. Others have proposed that Giardia attachment results in repopulation of the intestinal epithelium by relatively immature enterocytes with reduced absorptive capacities (leading to diarrhea).

• #24 Giardiasis: What It Is, Symptoms, Treatments & Medications

  https://my.clevelandclinic.org/health/diseases/15238-giardiasis

  Giardia infection doesn’t always cause noticeable symptoms, but it can. Some symptoms are due to the parasite itself, and others are due to your body activating to remove the parasite. For example, the parasite feeding off your nutrients might sap your energy, making you feel increasingly tired. Diarrhea, swelling and skin reactions are symptoms of inflammation, part of your immune system’s response. […] If giardiasis lasts a long time, it can damage the lining of your small intestine. This can cause chronic gastrointestinal symptoms and trigger irritable bowel syndrome. It can also damage your intestines’ ability to absorb the nutrients in your food. You could develop nutritional deficiencies. This could affect growth and development in children. […] In some people with severe and/or chronic giardiasis, long-term inflammation triggers an autoimmune response. This means that part of your immune response to the infection becomes hyperactive and automatic, continuing even after the infection is gone. Some people have developed reactive arthritis, chronic fatigue syndrome or new food allergies.

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