The Key Laboratory of Innate Immune Biology of Fujian Province, Biomedical Research Center of South China, College of Life Sciences, Fujian Normal University, Fuzhou, China.
Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Nat Immunol. 2016 Sep 20;17(10):1142-9. doi: 10.1038/ni.3558.
The recognition of microbial nucleic acids is a major mechanism by which the immune system detects pathogens. Cyclic GMP-AMP (cGAMP) synthase (cGAS) is a cytosolic DNA sensor that activates innate immune responses through production of the second messenger cGAMP, which activates the adaptor STING. The cGAS-STING pathway not only mediates protective immune defense against infection by a large variety of DNA-containing pathogens but also detects tumor-derived DNA and generates intrinsic antitumor immunity. However, aberrant activation of the cGAS pathway by self DNA can also lead to autoimmune and inflammatory disease. Thus, the cGAS pathway must be properly regulated. Here we review the recent advances in understanding of the cGAS-STING pathway, focusing on the regulatory mechanisms and roles of this pathway in heath and disease.
微生物核酸的识别是免疫系统检测病原体的主要机制。环鸟苷酸-腺苷酸合酶 (cGAS) 是一种细胞质 DNA 传感器，通过产生第二信使 cGAMP 激活先天免疫反应，cGAMP 激活衔接蛋白 STING。cGAS-STING 途径不仅介导了针对多种含有 DNA 的病原体感染的保护性免疫防御，还检测肿瘤源性 DNA 并产生内在的抗肿瘤免疫。然而，自身 DNA 的 cGAS 途径异常激活也可导致自身免疫和炎症性疾病。因此，cGAS 途径必须得到适当的调节。本文综述了近年来对 cGAS-STING 途径的理解进展，重点介绍了该途径在健康和疾病中的调节机制和作用。
