DNA has been known to be a potent immune stimulus for more than half a century. However, the underlying molecular mechanisms of DNA-triggered immune response have remained elusive until recent years. Cyclic GMP-AMP synthase (cGAS) is a major cytoplasmic DNA sensor in various types of cells that detect either invaded foreign DNA or aberrantly located self-DNA. Upon sensing of DNA, cGAS catalyzes the formation of cyclic GMP-AMP (cGAMP), which in turn activates the ER-localized adaptor protein MITA (also named STING) to elicit the innate immune response. The cGAS-MITA axis not only plays a central role in host defense against pathogen-derived DNA but also acts as a cellular stress response pathway by sensing aberrantly located self-DNA, which is linked to the pathogenesis of various human diseases. In this review, we summarize the spatial and temporal mechanisms of host defense to cytoplasmic DNA mediated by the cGAS-MITA axis and discuss the association of malfunctions of this axis with autoimmune and other diseases.

中文翻译：

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对细胞质 DNA 的先天免疫反应：机制和疾病。

半个多世纪以来，人们都知道 DNA 是一种有效的免疫刺激物。然而，直到最近几年，DNA 触发的免疫反应的潜在分子机制仍然难以捉摸。环 GMP-AMP 合酶 (cGAS) 是各种类型细胞中的主要细胞质 DNA 传感器，可检测入侵的外源 DNA 或异常定位的自身 DNA。在检测到 DNA 后，cGAS 会催化环 GMP-AMP (cGAMP) 的形成，进而激活 ER 定位的接头蛋白 MITA（也称为 STING）以引发先天免疫反应。cGAS-MITA 轴不仅在宿主对病原体衍生 DNA 的防御中发挥核心作用，而且还通过感知异常定位的自身 DNA 充当细胞应激反应途径，这与各种人类疾病的发病机制有关。在这次审查中，