Type I IFN operates pyroptosis and necroptosis during multidrug-resistant A. baumanniiinfection

Multidrug-resistant Acinetobacter baumannii, a common pathogen responsible for nosocomial infections, is the main cause for outbreaks of infectious diseases, such as pneumonia, meningitis, and bacteremia, especially among critically ill patients. Epidemic A. baumanniiis a growing public health concern as it is resistant to all existing antimicrobial agents, thereby necessitating the development of new therapeutic approaches to mount an effective immune response against this bacterial pathogen. In this study, we identified a critical role for type I interferon (IFN) in epigenetic regulation during A. baumanniiinfection and established a central role for it in multiple cell death pathways. A. baumanniiinfection induced mixed cell death constituted of apoptosis, pyroptosis, and necroptosis. Mechanically, A. baumanniitriggered TRIF-dependent type I IFN production, which in turn induced the expression of genes Zbp1, Mlkl, caspase-11, and Gsdmdvia KAT2B-mediated and P300-mediated H3K27ac modification, leading to NLRP3 inflammasome activation, and potentially contributed to GSDMD-mediated pyroptosis and MLKL-dependent necroptosis. Our study offers novel insights into the mechanisms of type I IFN and provides potential therapeutic targets for infectious and inflammatory diseases.