Deficiency of NRF2 predisposes mice to Pseudomonas aeruginosa induced pneumonia

Rationale: Pseudomonas aeruginosa is the most common gram‐negative organism associated with hospital acquired pneumonia. NRF2 maintains cellular redox homeostasis by regulating antioxdative genes, and it protects from oxidative stress and dysregulation of the innate immune response. We have previously demonstrated increased mortality of NRF2−/− mice to endotoxin mediated septic shock and cecal ligation and puncture‐mediated polymicrobial sepsis. The present study was designed to investigate the role of NRF2 in P. aeruginosa induced pneumonia and mortality. Methods: NRF2−/− and wild type mice were administered with P.aeruginosa intranasally. Mortality, pulmonary inflammation, and bacterial counts were measured. Results: P.aeruginosa caused greater and earlier mortality in NRF2−/− mice, compared to wild‐type mice. Lungs of NRF2−/− mice were associated with enhanced neutrophil recruitment, compared to wild‐type mice. Lungs from NRF2−/− mice contained increased bacterial counts, and were associated with significantly lower antioxidative gene expression and increased oxidative stress. Conclusion: NRF2 plays a central role in protecting from P. aeruginosa‐induced pneumonia and mortality.