<i>Giardia muris</i> Protection against <i>Citrobacter rodentium C</i> olitis is Associated with Inflammasome Activation and Increased Release of Antimicrobial Peptides in the Gut
Bibliographic record
Abstract
Background Polymicrobial gastrointestinal (GI) infections are common in individuals living in areas with poor sanitation. In areas where Giardia sp. infections are found in association with enteropathogens causing diarrhea via gut inflammation, Giardia sp. appears to protect against diarrhea via mechanisms that remain unlcear. Intestinal epithelial anti‐microbial peptides (AMPs) and the canonical and non‐canonical inflammasome pathways are essential to host defense. Objectives The aim of this study was to determine whether Giardia muris infection may protect against C itrobacter rodentium colitis, and whether this involves inflammasome activation and/or enhanced AMP production. Methods Male C57BL/6 mice were co‐infected with G. muris trophozoites and GFP‐labeled C. rodentium . Animals were assessed for weight gain, fecal blood, histopathology, myeloperoxidase (MPO) assays, bacterial loads, immunofluorescence for microbial‐tissue interactions, as well as Western blotting and qPCR for caspase‐1 and ‐11 (markers of inflammasome activation), β‐Defensin‐2 and Trefoil‐Factor (TFF) 3. Results At 14 days post‐infection, mice infected with C. rodentium had increased macroscopic damage in colon, lost weight and rectal bleeding; G. muris co‐infection significantly inhibited these effects. Microscopic damage score and MPO levels were reduced in co‐infected animals at 14 days post‐infection. In the colon of C. rodentium ‐infected mice, we observed attachment of bacteria to the intestinal epithelium and translocation into the lamina propria. In Giardia co‐infected animals, mucosal adhesion and translocation of C. rodentium was reduced and associated with lower tissue C. rodentium counts. Colonic caspase‐1 and ‐11 protein levels were increased in the co‐infected group compared to animals given C. rodentium alone. In colonic tissues of mice co‐infected with G. muris , mRNA and protein levels of the AMPs β‐Defensin‐2 and TFF3 proteins were significantly increased compared to animals given C. rodentium alone. Immunofluorescence of colonic tissues revealed increased intensity of TFF3 and β‐Defensin‐2 in co‐infected animals, particularly in the lumen and intestinal epithelium. Conclusion The data indicate that G. muris infection protects against C. rodentium‐ ‐induced colitis, in association with upregulation of intestinal AMPs and activation of inflammasome pathways. Our data shed new light on how microbial‐microbial interactions may protect against bacterial enteritis in zones endemic for giardiasis. Support or Funding Information This work was supported by Canadian Institutes of Health Research
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".