Advances in structure-guided mechanisms impacting on the cGAS–STING innate immune pathway

The metazoan cGAS–STING innate immunity pathway is triggered in response to cytoplasmic double-stranded DNA (dsDNA), thereby providing host defense against microbial pathogens. This pathway also impacts on autoimmune diseases, cellular senescence and anti-tumor immunity. The cGAS–STING pathway was also observed in the bacterial antiviral immune response, known as the cyclic oligonucleotide (CDN)-based anti-phage signaling system (CBASS). This review highlights a structure-based mechanistic perspective of recent advances in metazoan and bacterial cGAS–STING innate immune signaling by focusing on the cGAS sensor, cGAMP second messenger and STING adaptor components, thereby elucidating the specificity, activation, regulation and signal transduction features of the pathway.