A240 THE PROTECTIVE EFFECT OF <i>HYMENOLEPIS DIMINUTA</i> INFECTION IN EXPERIMENTAL COLITIS CAN BE INDEPENDENT OF IL-4RΑ SIGNALING
Bibliographic record
Abstract
Abstract Background Helminth parasites are potent inducers of Th2 immunity, characterized by the production of IL-4, IL-5, IL-13 and IL-10, and mobilization of regulatory cells. This orchestrated immune response establishes an immunomodulatory and/or immunosuppressive environment that may be protective against colitis and other inflammatory diseases. Earlier studies reveal that infection with the tapeworm parasite Hymenolepis diminuta ameliorates chemical-induced colitis in immunocompetent mice, and highlighted participation of the anti-inflammatory cytokine IL-10 in the mechanisms of protection. Moreover, the IL-4ra/STAT6 signaling pathway plays a pivotal role in promoting the Th2 immune response that is crucial for parasite expulsion: IL-4ra KO mice cannot expel the worm. However, the need for activation of IL-4rasignaling in the suppression of colitis by H. diminuta infection is unknown. Aims To determine if the inhibition of DNBS-induced colitis evoked by infection with H. diminuta requires IL-4ra signaling. Methods IL-4ra KO mice (n=4-8/group) were orally infected with 5 viable cysticercoids of H. diminuta and 8 days post-infection (dpi) were treated with 2.5 mg of dinitrobenzene sulfonic acid (DNBS). Subsequently, mice were assessed 72h post-DNBS. Disease was assessed by macroscopic disease activity score, colon length, weight loss, MPO activity of the colon, and leucocyte profile by blood count. Production of IL-10 by concanavalin-A (con-A; 48h)-stimulated splenocytes was measured by ELISA. Results An increase in blood eosinophilia in H. diminuta infected mice indicated a successful infection. DNBS treatment induced acute colitis in IL-4ra KO mice, and surprisingly prior infection with H. diminuta resulted in significantly less severe colitis, as evidenced by reduction in macroscopic disease activity score, prevention of weight loss, reduced MPO colon levels and maintenance of regular colon length. However, splenocytes from H. diminuta-infected IL-4ra KO mice did not show increased IL-10 production evoked by con-A compared to cells from non-infected mice. Conclusions These results indicate that the protection against DNBS-induced colitis by prior infection with H. diminuta can occur in the absence of IL-4ra signalling. This suggests redundancy in the anti-colitic effect of infection with this helminth parasite, such that absence of IL4ra is compensated for via another, yet to be determined, mechanism. We speculate that this may be via participation of type 2 innate lymphoid cell activity, mobilization of regulatory T cells or innate immunity: all possibilities that need to be rigorously tested. Funding Agencies CIHRBeverly Phillips Rising Star and Cumming School of Medicine (U. Calgary) Fellowships
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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) | 0.005 | 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".