A162 INTERLEUKIN-4 SIGNALING IS NOT A PREREQUISITE FOR HELMINTH-THERAPY PROTECTION AGAINST COLITIS
Bibliographic record
Abstract
Abstract Background Infection with helminth parasites drives Th2 immunity, characterized by the cytokines IL-4, -5, -13, and IL-10, and expansion of regulatory cells. These orchestrated immune responses promote an immunomodulatory/immunosuppressive environment, which can protect the host from concomitant inflammation. Mice infected with the tapeworm Hymenolepis diminuta display a strong Th2 immune response and they are protected from DNBS-induced colitis. Surprisingly, preliminary data indicated that il-4ra-/- mice (where the worm establishes) were protected from DNBS-induced colitis. Here we sought to confirm or refute the findings in il-4ra-/- and, if positive, investigate the role of IL-10 and macrophages in the anti-colitic effect. Aims To determine if IL-10 and macrophages play key roles in the protection against colitis in il-4ra-/- mice infected with H. diminuta. Methods BALB/c (WT) and il-4ra-/- mice (IL-4ra-/-) (n=4-15/group) were orally infected with 5 cysticercoids of H. diminuta and 8 days post-infection (dpi) were treated with 2.5 mg of dinitrobenzene sulfonic acid (DNBS) to induce colitis. In some experiments, mice were treated 3 times i.p. with neutralizing anti-IL10 antibody (100 mg/mouse) or clodronate-liposomes (100 ml/mouse) to deplete macrophages (5 days and 24h before and after DNBS). Mice were necropsied 72h post-DNBS and disease was assessed through macroscopic disease activity score (DAS), colon length, weight loss, colonic MPO activity, blood leucocyte profile and histopathological score. Cytokine production by antigen-specific (H.d. antigen 200mg/mL; 48h) stimulated splenocytes was measured by ELISA. Results DNBS treatment induced colitis in WT and IL-4ra-/- and prior infection with H. diminuta was anti-colitic in both groups as shown by reduced DAS, weight loss, MPO activity, and histopathology. Compared to WT, il-4ra-/- mice had less blood eosinophilia, and il-5 and il-10 production by worm-antigen stimulated splenocytes, although il-10 production was increased compared to splenocytes from uninfected control mice. Immunoneutralization of il-10 and macrophage depletion abolished the protective effects of infection with H. diminuta, with the clondronate-treated mice displaying severe disease. Conclusions Despite harbouring a patient infection with H. diminuta, il-4ra-/- mice are protected from DNBS-induced colitis that is, at least in part dependent on IL-10 and likely a phenotype of regulatory macrophage. The data suggest redundancy in the anti-colitic effects of H. diminuta infection, such that absence of il-4ra is compensated for via other, yet to be determined, mechanisms. Funding Agencies CAG, CIHRTRIANGLE
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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) | 0.001 | 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) | 0.006 | 0.002 |
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".