The pro-inflammatory and anti-inflammatory TLR2 responses to <i>Staphylococcus aureus</i> can be uncoupled (P1242)
Bibliographic record
Abstract
Abstract Microbial detection by pattern recognition receptors (PRRs) is typically associated with a pro-inflammatory cytokine response that primes adaptive immunity. However, some PRRs may also elicit an anti-inflammatory response. Most notably, LPS engagement to Toll-like receptor 4 (TLR4) leads to a PI3K-dependent internalization of TLR4, and the production of Type I interferons and, subsequently, of the anti-inflammatory cytokine IL-10. We have previously reported that peptidoglycan-embedded molecules in the gram-positive bacterium Staphylococcus aureus cell wall, acting on TLR2 on monocytes and macrophages, trigger a PI3K/Akt-dependent IL-10 response that can suppress adaptive T cell immunity. We now report that, unlike the anti-inflammatory TLR4 response, the TLR2-mediated anti-inflammatory IL-10 response is independent of actin-mediated receptor internalization and Type I interferon production. More importantly, the anti-inflammatory response triggered by S. aureus isolates through TLR2 can be uncoupled from the pro-inflammatory response, as they have different kinetics and TLR2 internalization requirements. Our data reveal a novel mechanism of TLR-mediated anti-inflammatory response that may be triggered by selective ligands on the staphylococcal cell wall. Identification of these anti-inflammatory TLR2 ligands may be a first step toward designing novel therapies to treat staphylococcal infections.
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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".