Eaglesham James B, Kranzusch Philip J
Department of Microbiology, Harvard Medical School, Boston, MA 02115, USA; Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA 02115, USA; Harvard PhD Program in Virology, Division of Medical Sciences, Harvard University, Boston, MA 02115, USA.
Department of Microbiology, Harvard Medical School, Boston, MA 02115, USA; Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA 02115, USA; Harvard PhD Program in Virology, Division of Medical Sciences, Harvard University, Boston, MA 02115, USA; Parker Institute for Cancer Immunotherapy at Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Curr Opin Immunol. 2020 Oct;66:27-34. doi: 10.1016/j.coi.2020.04.002. Epub 2020 Apr 15.
The cyclic GMP-AMP synthase (cGAS)- Stimulator of Interferon Genes (STING) pathway of cytosolic DNA sensing allows mammalian cells to detect and respond to infection with diverse pathogens. Pathogens in turn encode numerous factors that inhibit nearly all steps of cGAS-STING signal transduction. From masking of cytosolic DNA ligands, to post-translational modification of cGAS and STING, and degradation of the nucleotide second messenger 2'3'-cGAMP, pathogens have evolved convergent mechanisms to evade cGAS-STING sensing. Here we examine pathogen inhibitors of innate immunity in the context of newly discovered regulatory features controlling cellular cGAS-STING activation. Comparative analysis of these strategies provides insight into mechanisms of action and suggests aspects of cGAS-STING regulation and immune evasion that remain to be discovered.
胞质DNA感应的环磷酸鸟苷-腺苷酸合成酶（cGAS）-干扰素基因刺激物（STING）途径使哺乳动物细胞能够检测并应对多种病原体的感染。反过来，病原体编码了许多因子，这些因子几乎抑制了cGAS-STING信号转导的所有步骤。从胞质DNA配体的掩盖，到cGAS和STING的翻译后修饰，以及核苷酸第二信使2'3'-cGAMP的降解，病原体已经进化出趋同机制来逃避cGAS-STING感应。在这里，我们在新发现的控制细胞cGAS-STING激活的调控特征的背景下研究病原体对先天免疫的抑制剂。对这些策略的比较分析提供了对作用机制的深入了解，并暗示了cGAS-STING调控和免疫逃避中仍有待发现的方面。
