Cleavage of interleukin‐8 and attenuation of neutrophil chemotaxis by a <i>Giardia</i> cathepsin B
Bibliographic record
Abstract
Parasitic immunomodulatory molecules are currently undergoing investigation for their potential as anti‐inflammatory therapeutics. Children infected with the small intestinal parasite Giardia duodenalis have attenuated inflammatory responses via unknown mechanisms. Objective To determine if Giardia trophozoites modulate interleukin‐8 (CXCL8) secretion from intestinal epithelial cells (IECs) resulting in attenuated neutrophil (PMN) chemotaxis. Results Co‐incubation of Giardia trophozoites with ex vivo small intestinal mucosal biopsy tissues or in vitro monolayers resulted in attenuation of IL‐1β‐ or S. typhimurium‐ induced CXCL8 secretion via parasitic cleavage of CXCL8. Giardia ‐mediated cleavage of CXCL8 decreased its chemotactic ability for PMNs. Giardia trophozoites secrete cysteine proteases in the presence or absence of in vitro monolayers. Inhibition of Giardia cysteine proteases with a cysteine protease inhibitor (E‐64d) or a cathepsin B‐specific inhibitor (Ca‐074Me) inhibited Giardia ‐mediated cleavage of CXCL8. Conclusion Giardia trophozoites release a cathepsin B‐like protease that cleaves CXCL8 and attenuates PMN chemotaxis. 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) | 0.000 | 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 | 0.001 |
| 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".