Effect of chronic Giardia lamblia infection on epithelial transport and barrier function in human duodenum

Troeger, Hanno; Epple, Hans-Joerg; Schneider, Thomas; Wahnschaffe, Ulrich; Ullrich, Reiner; Burchard, Gerd‐Dieter; Jelı́nek, Tomáš; Zeitz, Martin; Fromm, Michael; Schulzke, Joerg-Dieter

doi:10.1136/gut.2006.100198

Cited by 233 publications

(225 citation statements)

References 45 publications

(41 reference statements)

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“…Other studies also found that Giardia disrupts enterocyte alpha-actinin, a component of the actomyosin ring that regulates paracellular flow across intestinal epithelia (Teoh et al, 2000). Consistent with these observations, the parasite also affects epithelial claudin proteins, which are critical components of the sealing properties of tight junctions; these alterations have been shown to disrupt intestinal barrier function in human giardiasis (Troeger et al, 2007). Together, the findings available to date indicate that Giardia-induced enterocyte apoptosis is responsible for increased intestinal permeability during the infection.…”

Section: Loss Of Epithelial Barrier Functionmentioning

confidence: 57%

“…Symptoms can be present in the absence of any significant morphologic injury to the intestinal cleavage, down-regulation of anti-apoptotic Bcl-2, and increased expression of pro-apoptotic Bax (Panaro et al, 2007). Studies in human patients with chronic giardiasis have now confirmed that infection with Giardia duodenalis is indeed associated with increased rates of enterocyte apoptosis (Troeger et al, 2007). Giardia can also prevent the formation of epithelial 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 (Eckmann et al, 2000).…”

Section: Mechanisms Of Heightened Enterocytic Apoptosis and Anti-apopmentioning

confidence: 99%

“…Moreover, infection with Giardia duodenalis in gerbils has been associated with elevated macromolecular uptake in the jejunum during the period of peak trophozoite colonization, but not during the parasite clearance phase (Hardin et al, 1997). It was recently demonstrated that chronic giardiasis is also responsible for a loss of intestinal barrier function in human infections (Troeger et al, 2007). Increased epithelial permeability allows luminal antigens to activate host immune-dependent pathological pathways.…”

Section: Loss Of Epithelial Barrier Functionmentioning

confidence: 99%

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Pathophysiology of enteric infections withGiardia duodenalis

Buret

2008

Parasite

120

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Summary :Giardia is the most prevalent human intestinal parasitic protist in the world, and one of the most common parasite of companion animals and young livestock. Giardia is a major cause of diarrhea in children and in travelers. The host-microbial interactions that govern the outcome of infection remain incompletely understood. Findings available to date indicate that the infection causes diarrhea via a combination of intestinal malabsorption and hypersecretion. Malabsorption and maldigestion mainly result from a diffuse shortening of epithelial microvilli. This 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. Recent findings suggest that these effects may facilitate the development of chronic enteric disorders, including inflammatory bowel disease, irritable bowel syndrome, and allergies, via mechanisms that remain poorly understood. A newly discovered SGLT-1 glucose uptake-mediated host cytoprotective mechanism may represent an effective modulator of the epithelial apoptosis induced by this parasite, and, possibly, by other enteropathogens. A better understanding of the pathogenesis of giardiasis will shed light on new potential therapeutic targets.

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Section: Loss Of Epithelial Barrier Functionmentioning

confidence: 57%

Section: Mechanisms Of Heightened Enterocytic Apoptosis and Anti-apopmentioning

confidence: 99%

Section: Loss Of Epithelial Barrier Functionmentioning

confidence: 99%

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Pathophysiology of enteric infections withGiardia duodenalis

Buret

2008

Parasite

120

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“…Trophozoites use ADI and OCT to actively metabolize arginine for energy, thus depleting arginine from the growth medium. Arginine depletion is known to induce apoptosis in human cell lines [40] and human giardiasis patients show an increased rate of apoptosis of intestinal epithelial cells [23]. This has been suggested to be a major disease mechanism [22].…”

Section: Discussionmentioning

confidence: 99%

“…Recently several cysteine-type proteases of G. lamblia origin were detected after co-incubations with rat small intestine epithelial cells [15], and other host cell-Giardia interaction experiments and giardiasis patient data have shown that Giardia reduces the epithelial barrier function [16,17] and induces apoptosis [14,[21][22][23], but the effector protein(s) have never been identified. To improve our understanding of host-parasite interactions during infection, we asked whether exposure of G. lamblia to human intestinal epithelial cells (IEC) might lead to release of trophozoite proteins into the medium.…”

Section: Introductionmentioning

confidence: 99%

Release of metabolic enzymes by Giardia in response to interaction with intestinal epithelial cells

Ringqvist

Palm

Skarin

et al. 2008

Molecular and Biochemical Parasitology

154

139

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Giardia lamblia, an important cause of diarrheal disease, resides in the small intestinal lumen in close apposition to epithelial cells. Since the disease mechanisms underlying giardiasis are poorly understood, elucidating the specific interactions of the parasite with the host epithelium is likely to provide clues to understanding the pathogenesis. Here we tested the hypothesis that contact of Giardia lamblia with intestinal epithelial cells might lead to release of specific proteins. Using established co-culture models, intestinal ligated loops and a proteomics approach, we identified three G. lamblia proteins (arginine deiminase, ornithine carbamoyl transferase and enolase), previously recognized as immunodominant antigens during acute giardiasis. Release was stimulated by cell-cell interactions, since only small amounts of arginine deiminase and enolase were detected in the medium after culturing of G. lamblia alone. The secreted G. lamblia proteins were localized to the cytoplasm and the inside of the plasma membrane of trophozoites. Furthermore, in vitro studies with recombinant arginine deiminase showed that the secreted Giardia proteins can disable host innate immune factors such as nitric oxide production. These results indicate that contact of Giardia with epithelial cells triggers metabolic enzyme release, which might facilitate effective colonization of the human small intestine. a b s t r a c tGiardia lamblia, an important cause of diarrheal disease, resides in the small intestinal lumen in close apposition to epithelial cells. Since the disease mechanisms underlying giardiasis are poorly understood, elucidating the specific interactions of the parasite with the host epithelium is likely to provide clues to understanding the pathogenesis. Here we tested the hypothesis that contact of Giardia lamblia with intestinal epithelial cells might lead to release of specific proteins. Using established co-culture models, intestinal ligated loops and a proteomics approach, we identified three G. lamblia proteins (arginine deiminase, ornithine carbamoyl transferase and enolase), previously recognized as immunodominant antigens during acute giardiasis. Release was stimulated by cell-cell interactions, since only small amounts of arginine deiminase and enolase were detected in the medium after culturing of G. lamblia alone. The secreted G. lamblia proteins were localized to the cytoplasm and the inside of the plasma membrane of trophozoites. Furthermore, in vitro studies with recombinant arginine deiminase showed that the secreted Giardia proteins can disable host innate immune factors such as nitric oxide production. These results indicate that contact of Giardia with epithelial cells triggers metabolic enzyme release, which might facilitate effective colonization of the human small intestine.

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From celiac disease to coccidia infection and vice‐versa: The polyQ peptide CXCR3‐interaction axis

et al. 2021

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Zonulin is a physiological modulator of intercellular tight junctions, which upregulation is involved in several diseases like celiac disease (CeD). The polyQ gliadin fragment binds to the CXCR3 chemokine receptor that activates zonulin upregulation, leading to increased intestinal permeability in humans. Here, we report a general hypothesis based on the structural connection between the polyQ sequence of the immunogenic CeD protein, gliadin, and enteric coccidian parasites proteins. Firstly, a novel interaction pathway between the parasites and the host is described based on the structural similarities between polyQ gliadin fragments and the parasite proteins. Secondly, a potential connection between coccidial infections as a novel environmental trigger of CeD is hypothesized. Therefore, this report represents a promising breakthrough for coccidian research and points out the potential role of coccidian parasites as a novel trigger of CeD that might define a preventive strategy for gluten-related disorders in general. Also see the video abstract here: https://youtu.be/oMaQasStcFI

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Effect of chronic Giardia lamblia infection on epithelial transport and barrier function in human duodenum

Cited by 233 publications

References 45 publications

Pathophysiology of enteric infections withGiardia duodenalis

Pathophysiology of enteric infections withGiardia duodenalis

Release of metabolic enzymes by Giardia in response to interaction with intestinal epithelial cells

From celiac disease to coccidia infection and vice‐versa: The polyQ peptide CXCR3‐interaction axis

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