PTP1B preferentially regulates IRF7-ISRE-IFN pathway and negatively impacts host defense against <i>Pseudomonas aeruginosa</i> infection. (INM7P.348)
Bibliographic record
Abstract
Abstract Pseudomonas aeruginosais a major opportunistic pathogen in immune-compromised individuals. Toll-like receptors (TLRs) contribute to innate immunity against P. aeruginosa through activation of transcription factors IRF7/IRF3 and NFκB. However, mechanisms involved in the regulation of P. aeruginosa-induced TLR pathway activation remain incompletely defined. Here, we demonstrate that protein tyrosine phosphatase-1B (PTP1B) is a critical negative regulator in P. aeruginosa infection. PTP1B-deficient mice display greatly enhanced bacterial clearance which is accompanied with increased neutrophil infiltration and cytokine production. Interestingly, PTP1B-deficiency mainly up-regulates the production of IFN-stimulated response elements (ISRE)-regulated cytokines and chemokines including CCL5 (RANTES), CXCL10 (IP-10) and IFN-β production. Further studies reveal that PTP1B-deficiency leads to increased IRF7 activation. Importantly, PTP1B is physically associated with IRF7 in dendritic cells. These findings demonstrate a novel regulatory mechanism of the immune response to P. aeruginosa infection through PTP1B-IRF7 interaction. This novel PTP1B-IRF7-ISRE pathway may have broader implications in TLR-mediated innate immunity.
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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) | 0.004 | 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".