Identification of cGAS as an innate immune sensor of extracellular bacterium Pseudomonas aeruginosa
Chuan-min Zhou,
Biao Wang,
Qun Wu,
Ping Lin,
Shu-gang Qin,
Qin-qin Pu,
Xue-jie Yu,
Min Wu
Affiliations
Chuan-min Zhou
State Key Laboratory of Virology, School of Health Sciences, Wuhan University, Wuhan 430071, P.R. China; Department of Biomedical Sciences, University of North Dakota, Grand Forks, ND 58203-9037, USA; Zhongnan hospital of Wuhan University, Wuhan, Hubei Province, 430071, P. R. China
Biao Wang
Department of Biomedical Sciences, University of North Dakota, Grand Forks, ND 58203-9037, USA
Qun Wu
Department of Biomedical Sciences, University of North Dakota, Grand Forks, ND 58203-9037, USA
Ping Lin
Department of Biomedical Sciences, University of North Dakota, Grand Forks, ND 58203-9037, USA
Shu-gang Qin
Department of Biomedical Sciences, University of North Dakota, Grand Forks, ND 58203-9037, USA
Qin-qin Pu
Department of Biomedical Sciences, University of North Dakota, Grand Forks, ND 58203-9037, USA
Xue-jie Yu
State Key Laboratory of Virology, School of Health Sciences, Wuhan University, Wuhan 430071, P.R. China; Corresponding author
Min Wu
Department of Biomedical Sciences, University of North Dakota, Grand Forks, ND 58203-9037, USA; Corresponding author
Summary: Cyclic GMP-AMP synthase (cGAS) is reported essential for detecting intracellular bacteria. However, it remains to be determined whether and how cGAS is involved in extracellular bacterial infection. Here, we report that cGAS is essential for mediating type I interferon (IFN) production in infection by multiple extracellular pathogens, including Pseudomonas aeruginosa, Klebsiella pneumoniae, and Staphylococcus aureus. In addition, the canonical cGAS-stimulator of interferon gene (STING)-IFN axis is required for protecting mice from P. aeruginosa-induced mouse acute pulmonary infection, confirmed in cGAS pathway-specific gene deficiency mouse models. cGAS−/− and STING−/− mice exhibited reduced type I IFNs production, excessive inflammatory response accompanied with decreased resistance to P. aeruginosa challenge. Unfolded protein response was also modulated by cGAS through IRF3 and type I IFNs under P. aeruginosa infection. Collectively, these findings uncover the importance of cGAS in initiating immune responses against extracellular bacterial infection.
