摘要：SummaryCyclic 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, includingPseudomonas aeruginosa,Klebsiella pneumoniae, andStaphylococcus aureus.In addition, the canonical cGAS-stimulator of interferon gene (STING)-IFN axis is required for protecting mice fromP. aeruginosa-induced mouse acute pulmonary infection, confirmed in cGAS pathway-specific gene deficiency mouse models.cGAS−/−andSTING−/−mice exhibited reduced type I IFNs production, excessive inflammatory response accompanied with decreased resistance toP. aeruginosachallenge. Unfolded protein response was also modulated by cGAS through IRF3 and type I IFNs underP. aeruginosainfection. Collectively, these findings uncover the importance of cGAS in initiating immune responses against extracellular bacterial infection.Graphical AbstractDisplay OmittedHighlights•The role of cGAS signaling pathway is expanded in sensing extracellular bacteria•cGAS/STING/IFNARaxis is necessary host immunity restrictingP. aeruginosa•cGAS signaling pathway is involved in modulating unfolded protein response•cGAS is an important nucleic acids' sensor in recognizing extracellular bacteriaImmune Response; Microbiology; Bacteriology
