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. baumannii is 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. baumannii infection and established a central role for it in multiple cell death pathways. A. baumannii infection induced mixed cell death constituted of apoptosis, pyroptosis, and necroptosis. Mechanically, A. baumannii triggered TRIF-dependent type I IFN production, which in turn induced the expression of genes Zbp1, Mlkl, caspase-11, and Gsdmd via 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.
[1]Chinese Acad Sci, Key Lab Anim Models & Human Dis Mechanisms, Kunming 650223, Yunnan, Peoples R China.
[2]Chinese Acad Sci, Kunming Inst Zool, Key Lab Bioact Peptides Yunnan Prov, Kunming 650223, Yunnan, Peoples R China.
[3]Kunming Med Univ, Affiliated Hosp 1, Dept Clin Lab, 295 Xichang Rd, Kunming 650032, Yunnan, Peoples R China.
[4]Zhejiang Univ, Sch Med, Inst Immunol, Hangzhou 310058, Zhejiang, Peoples R China.
[5]Shanghai Jiao Tong Univ, Sch Med, Inst Med Sci, Shanghai Inst Immunol, Shanghai, Peoples R China.
[6]St Jude Childrens Res Hosp, Dept Tumor Cell Biol, Canc Biol Program, Memphis, TN 38105 USA.
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