Long Pentraxin 3 (PTX3) Regulates IL-17A Mediated Immunity to Primary and Secondary <i>Leishmania major</i> Infection
Bibliographic record
Abstract
Abstract Resolution of cutaneous leishmaniasis (CL), caused by the protozoan parasite Leishmania (L) major, relies on the nature of the host immune response. The long pentraxin 3 (PTX3), a soluble pattern recognition molecule, is critical for wound healing by regulating tissue repair and also in innate and adaptive responses during infection and inflammation. Here, we show that PTX3 regulates disease pathogenesis and immunity to CL. PTX3 expression is increased in active skin lesions in patients and mice during CL, with higher levels being expressed in individuals with severe disease. PTX3−/− mice were highly resistant to primary and secondary L. major infection. Interestingly, the enhanced resistance of PTX3−/− mice to primary or secondary L. major infection was not associated with enhanced IFN-γ or decreased IL-10 response. Instead, L. major-infected PTX3−/− mice displayed strong IL-17 response and in vivo neutralization of IL-17A abolished their enhanced resistance. Naïve CD4+ T cells from PTX3−/− mice displayed increased differentiation into Th17 cells and this was associated with increased expression of Th17-specific transcription factors including RORγt, AhR and STAT3. Addition of recombinant PTX3 significantly inhibited the expression of Th17-specific transcription factors and the frequency of Th17 cells in Th17 polarizing cultures of PTX3−/− CD4+ T cells. Similarly, healed PTX3−/− mice had higher frequencies of effector memory CD4+ T cells that rapidly proliferate and differentiate into IL-17A-producing CD4+ T cells upon secondary challenge. Collectively, our results show that PTX3 contributes to pathogenesis of CL by negatively regulating protective Th17 and IL-17 responses.
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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 | 0.001 | 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 | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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".