期刊
ANNUAL REVIEW OF IMMUNOLOGY, VOL 38
卷 38, 期 -, 页码 79-98出版社
ANNUAL REVIEWS
DOI: 10.1146/annurev-immunol-070119-115052
关键词
DNA; cell compartment; viral infection; innate immunity; type I interferons; cGAS; MITA/STING; immune diseases
类别
资金
- State Key R&D Program of China [2017YFA0505800, 2016YFA0502102]
- National Natural Science Foundation of China [31830024, 31630045]
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.
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