The phenotype and wound healing property of IL‐4‐treated human macrophages is not affected by co‐treatment with antigen from the tapeworm, <i>Hymenolepis diminuta</i>
Bibliographic record
Abstract
Background Infection with parasitic helminths can reduce inflammation in animal models of colitis. A component of this anti‐inflammatory effect may be induction of alternatively‐activated IL‐4 driven anti‐inflammatory/pro‐resolution macrophages (M(IL4)) that have been implicated in wound repair. Infection with helminth parasites or exposure to worm extracts may elicit unique macrophage phenotypes. We hypothesized that macrophages co‐treated with IL‐4 and a crude extract Hymenolepis diminuta (HdE), would have an enhanced ability to promote repair in wounded epithelial monolayers. Aim To assess the impact of HdE on the development of human and murine M(IL4)s using canonical markers and assess the ability of these cells to promote epithelial wound repair. Methods Human (blood‐derived) and murine (bone marrow‐derived) macrophages were exposed to IL‐4 (10 ng/ml; 48h), HdE (100 mg/ml; 48h), IL4+HdE, or left unstimulated (controls). Expression of M(IL4) markers were assessed by qPCR, immunoblotting or ELISA (human: CD206, CCL18, CD14; murine: arginase‐1, Ym1). Confluent Caco2 epithelial cell monolayers were wounded with a razor blade and treated with supernatants from the different human macrophage sub‐types populations; protein denatured (trypsin‐treated + boiling) were also used. The total area of epithelial migration was measured (in mm 2 ) 24h later. TGFb levels in the macrophage supernatants were measured by ELISA. Results The development of human M(IL4)s was not affected by HdE co‐treatment as assessed by any of the markers examined, whereas HdE did reduce arginase‐1 and Ym1 in murine M(IL4)s (n=4–6). Supernatants from M(IL4)s increased epithelial migration by 36% ± 14% (n=8, p<0.05) compared to baseline, and this was not affected by HdE co‐treatment of the macrophages. Protein denaturing ablated the ability of M(IL4) supernatant to enhance epithelial wound repair (n=6). TGFb levels were increased in M(IL4) supernatants (353 ± 78*) compared to those from non‐stimulated macrophages (204 ± 71 pg/ml) (n=11; *p<0.05 (paired t test)). Conclusion HdE has negligible effects on the induction of a human M(IL4) and does not inhibit its ability to promote epithelial wound repair, that could be TGFb dependent. Thus, (1) M(IL4)s elicited in humans following infection with helminths will not be adversely affected by the release of worm antigen, and (2) if an anti‐colitic effect of systemic delivery of helminth antigens to humans results in mobilization of an IL‐4‐type alternatively activated macrophage, this would be an indirect effect of the worm antigen. Support or Funding Information Supported by Crohn's Colitis Canada grant to DMM and an NSERC CREATE Host‐Parasite Interactions scholarship to Timothy Jayme
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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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.003 | 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".