IFN-γ mediated epithelial injury during influenza pathogenesis

Abstract Influenza pneumonia is developed due to an exuberant host response accompanied by impaired repair, causing profound airway lung and vascular injuries that impact gas exchange require hospitalization. However, a significant knowledge gap remains in delineating the mechanisms regulating intricate inflammatory balance either favor viral clearance or develops into immune-mediated pathology. Substantial emerging data reveal dysregulated interferon (IFN) signaling, including excessive IFN-II (IFN-g) production, promotes injury impairs repair during influenza pathogenesis. In our ongoing work, we have discovered IFN-g exerts direct pathologic effect promoting epithelial resulting exacerbation of pulmonary inflammation loss barrier integrity influenza. The notable findings from study are as follows. a.IFN-g causes cell death infected (IAV) un-infected (bystander) alveolar cells at comparable rate, contributing disruption barrier. b.Molecularly , identified suppressed IL6-STAT3 axis, which protective against injury. c.Notably, deficiency was abrogated neutralizing IL-6. d.Finally, using vitrohuman mouse show IL-6 treatment can ameliorate mediated IAV-infected (bystander injury). Our first demonstrate suppression IL-6-STAT3 axis potential molecular basis best understanding. National Institute Health