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

Abstract

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.