Properdin mediates complement activation and is protective against infectious colitis (902.6)
Bibliographic record
Abstract
Background: Properdin amplifies complement activation and also acts as a pattern recognition receptor, facilitating the removal of microbes and apoptotic/necrotic cells in complement‐dependent and ‐independent mechanisms. C. rodentium is a natural bacterial pathogen of mice leading to colitis; we asked if properdin plays a role during C. rodentium colitis. Methods: C. rodentium was gavaged into C57BL/6 (wildtype, WT) or properdin gene knockout (P‐/‐) mice and colitis was quantified by histopathological scoring of the colon and measurements of inflammatory mediators and apoptosis. In some experiments WT or P‐/‐ serum was injected into infected mice and the effects on colitis assessed. Results: C. rodentium infected P‐/‐ mice exhibited levels of gut C3a higher than in infected WT mice but significantly less C5a than in WT mice. P‐/‐ mice suffered exacerbated colonic inflammation compared to infected WT characterized by excessive ulceration, infiltration by CD4+ T cells, neutrophils and macrophages, and increased levels of interferon‐γ. Using immunofluorescence, properdin associated with apoptotic cells and infected P‐/‐ mice had increased numbers of apoptotic cells. Lastly, properdin sufficient serum resulted in increased C5a levels and fewer apoptotic cells associated with less inflammation. Conclusion: We discovered that properdin modulates complement activation during infectious colitis, evident by a lack of C5 convertase activity associated with a paradoxical increase in inflammation. We conclude that properdin regulates colitis in a C5a‐independent mechanism possibly related to a failure to remove apoptotic cell in the mucosa. Grant Funding Source : NSERC, CCFC
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| 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) | 0.000 | 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 teacher head, 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".