Giardia cathepsin B cysteine proteases degrade interleukin‐8 and attenuate interleukin‐8‐induced neutrophil chemotaxis (152.2)
Bibliographic record
Abstract
New therapeutic approaches for gastrointestinal inflammatory disorders are sorely needed. Children infected with the protozoan parasite Giardia duodenalis exhibit attenuated gut inflammatory responses via unknown mechanisms. The Giardia genome contains 9 cathepsin B (catB) proteases with anti‐inflammatory potential. Objectives. Using complimentary models of human intestinal biopsies, mice, and human enterocytes in vitro, to determine if Giardia infections attenuate Clostridium difficile toxin‐induced colitis, and if Giardia trophozoites attenuate interleukin‐8 (CXCL8) secretion from intestinal epithelial cells. Results. Reduced neutrophil (PMN) recruitment was observed in Giardia‐infected mice following rectal administration of C. difficile toxins. Co‐incubation of Giardia trophozoites with human small intestinal mucosal biopsy tissues ex vivo, or in vitro Caco‐2 monolayers resulted in attenuated of IL‐1β‐ or Salmonella‐induced CXCL8 secretion via catB‐mediated degradation of CXCL8. Giardia catB proteases also attenuated CXCL8‐induced PMN chemotaxis. Conclusion. Giardia trophozoites secrete catB proteases that degrade CXCL8 and attenuate CXCL8‐induced PMN chemotaxis. Parasitic protease‐mediated reduction of PMN’s may offer a promising therapeutic avenue for intestinal inflammatory disorders. Funding provided by NSERC, AIHS, and CCFC.
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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 | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
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".