The crosstalk between the caspase family and the cGAS-STING signaling pathway

Cytosolic nucleic acid sensors are critical for sensing nucleic acids and initiating innate immunity during microbial infections and/or cell death. Over the last decade, several key studies have characterized the conserved mechanism of cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS) and the downstream signaling adaptor stimulator of interferon genes (STING) initiating the innate immune signaling pathways. Aside from its primary involvement in microbial infections and inflammatory diseases, there is growing interest in the alternate roles of cGAS-STING-mediated signaling. Caspase family members are powerful functional proteins that respond to cellular stress, including cell death signals, inflammation, and innate immunity. Recent studies have uncovered how the caspase family cooperates with the cGAS-STING signaling pathway. Most caspase family members negatively regulate the cGAS-STING signaling pathway. In turn, some caspase family members can also be modulated by cGAS-STING. This review gives a detailed account of the interplay between the caspase family and the cGAS-STING signaling pathway, which will shed light on developing novel therapeutics targeting the caspase family and cGAS-STING signaling in antiviral innate immunity, cancer, inflammatory, and autoimmunity.

Automated summary

The manuscript discusses the role of cytosolic nucleic acid sensors during microbial infections and cell death, as well as the interaction between the caspase family and the cGAS-STING signaling pathway. This sheds light on novel therapeutic approaches targeting antiviral innate immunity, cancer, inflammatory diseases, and autoimmunity.