Fig. 1. Activation of the cGAS–STING signaling pathway to drive innate immune responses.

a cGAS is activated by mislocalized DNA in the cytosol by various sources such as self-DNA from damaged mitochondrion or micronucleus, or exogeneous DNA derived from virus, dead cell, and bacterium. Activated cGAS uses ATP and GTP as substrates to catalyze the formation of cGAMP, which acts as a second messenger to activate STING. b Cyclic dinucleotides secreted from bacteria can also activate STING directly. c Activated STING dimerizes and translocates from the ER to the perinuclear region via Golgi to recruit and promote TBK1-IRF3-IκB assembly, which subsequently drives activation of IRF3 and NF-κB to produce IFN and inflammatory cytokines (TNF, IL-6), respectively.