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.

中文翻译：

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cGAS-STING信号的进化起源

检测外来核酸是对病原体进行先天免疫识别的重要策略。在脊椎动物中，cGAS在胞质溶胶中感测到病原体衍生的DNA，后者产生环状二核苷酸（CDN）第二信使cGAMP以激活信号转接头STING。虽然在脊椎动物中诱导抗病毒I型干扰素（IFN）是STING活化的主要结果，但最近已经清楚地发现，cGAS-STING途径的核心成分已经进化了6亿多年前，早于I型IFN的进化。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。