Cytosolic nucleic acid sensors have a critical role in detecting endogenous nucleic acids to initiate innate immune responses during microbial infections and/or cell death. Several seminal studies over the past decade have delineated the conserved mechanism of cytosolic DNA sensor cyclic GMP-AMP synthase (cGAS) and the downstream signaling adapter stimulator of interferon genes (STING) in mediating innate immune signaling pathways as a host defense mechanism. Besides the predominant role in microbial infections and inflammatory diseases, there is an increased attention on alternative functional responses of cGAS–STING-mediated signaling. Here we review the complexity of interactions between the cGAS–STING signaling and cell death pathways. A better understanding of molecular mechanisms of this interplay is important with regard to the development of new therapeutics targeting cGAS–STING signaling in cancer, infectious, and chronic inflammatory diseases.

细胞质核酸传感器在检测内源性核酸以在微生物感染和/或细胞死亡期间启动先天免疫反应方面具有关键作用。过去十年中的几项开创性研究描绘了细胞溶质 DNA 传感器环 GMP-AMP 合酶 (cGAS) 和干扰素基因下游信号适配器刺激剂 (STING) 在介导先天免疫信号通路中作为宿主防御机制的保守机制。除了在微生物感染和炎症性疾病中的主要作用外，人们越来越关注 cGAS-STING 介导的信号传导的替代功能反应。在这里，我们回顾了 cGAS-STING 信号和细胞死亡途径之间相互作用的复杂性。