Division of Immunology and Pathogenesis, Department of Molecular and Cell Biology, University of California, Berkeley, CA, USA.
Division of Immunology and Pathogenesis, Department of Molecular and Cell Biology, University of California, Berkeley, CA, USA; Current Address: Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
Trends Immunol. 2017 Oct;38(10):733-743. doi: 10.1016/j.it.2017.03.004. Epub 2017 Apr 14.
Detection of foreign nucleic acids is an important strategy for innate immune recognition of pathogens. In vertebrates, pathogen-derived DNA is sensed in the cytosol by cGAS, which produces the cyclic dinucleotide (CDN) second messenger cGAMP to activate the signaling adaptor STING. While induction of antiviral type I interferons (IFNs) is the major outcome of STING activation in vertebrates, it has recently become clear that core components of the cGAS-STING pathway evolved more than 600 million years ago, predating the evolution of type I IFNs. Here we discuss the evolutionary origins of the cGAS-STING pathway, and consider the possibility that the ancestral functions of STING may have included activation of antibacterial immunity.
检测外来核酸是先天免疫识别病原体的一种重要策略。在脊椎动物中，cGAS 在细胞质中检测到病原体衍生的 DNA，cGAS 产生环二核苷酸 (CDN) 第二信使 cGAMP 来激活信号接头蛋白 STING。虽然 STING 激活在脊椎动物中诱导抗病毒 I 型干扰素 (IFN) 的产生是主要结果，但最近已经清楚，cGAS-STING 途径的核心组成部分早在 I 型 IFN 进化之前的 6 亿多年前就已经进化。在这里，我们讨论了 cGAS-STING 途径的进化起源，并考虑了 STING 的祖先功能可能包括激活抗菌免疫的可能性。
