The calcineurin-NFAT axis contributes to host defense during <i>Pseudomonas aeruginosa</i> lung infection
Bibliographic record
Abstract
Abstract Infection with the opportunistic pathogen Pseudomonas aeruginosa is effectively controlled through tightly coordinated inflammation in healthy individuals. Dysregulated inflammation in cystic fibrosis greatly increases susceptibility to P. aeruginosa and lung damage. Recently, we identified regulator of calcineurin-1, a small, conserved protein that suppresses the NFAT pathway by inhibition of calcineurin and functions as a central negative regulator of multiple inflammatory transcription factors after P. aeruginosa lung infection, implying a role for the canonical NFAT pathway in P. aeruginosa infection. Calcineurin is a calcium-calmodulin–responsive phosphatase that dephosphorylates NFAT and promotes NFAT nuclear translocation and transcriptional activity. The contribution of the NFAT pathway to host defense against P. aeruginosa remains poorly characterized. In this study, we found that NFAT was rapidly and transiently activated after P. aeruginosa infection both in vitro and in vivo. Deficiency of calcineurin Aβ caused impaired activation of NFAT and decreased inflammatory cytokine production in vivo. Finally, we demonstrated that the cross-talk between the NFAT and NFкB pathways coordinately transactivate host response genes during P. aeruginosa infection. Together, these results demonstrate for the first time that NFAT is activated through calcineurin and interacts with NFкB after P. aeruginosa lung infection, and contributes to the host inflammatory response.
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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 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 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".