炎症体
目标2
生物
先天免疫系统
细胞生物学
半胱氨酸蛋白酶1
DNA病毒
免疫系统
信号转导
炎症
免疫学
遗传学
基因
基因组
作者
Yutao Wang,Xiaohan Ning,Pengfei Gao,Shuangyan Wu,Mengyin Sha,Mengze Lv,Xiang Zhou,Juyi Gao,Run Fang,Guangxun Meng,Xiao‐Dong Su,Zhengfan Jiang
出处
期刊:Immunity
[Elsevier]
日期:2017-03-01
卷期号:46 (3): 393-404
被引量:186
标识
DOI:10.1016/j.immuni.2017.02.011
摘要
Viral infection triggers host innate immune responses that result in the production of various cytokines including type I interferons (IFN), activation of inflammasomes, and programmed cell death of the infected cells. Tight control of inflammatory cytokine production is crucial for the triggering of an effective immune response that can resolve the infection without causing host pathology. In examining the inflammatory response of Asc−/− and Casp1−/− macrophages, we found that deficiency in these molecules resulted in increased IFN production upon DNA virus infection, but not RNA virus challenge. Investigation of the underlying mechanism revealed that upon canonical and non-canonical inflammasome activation, caspase-1 interacted with cyclic GMP-AMP (cGAMP) synthase (cGAS), cleaving it and dampening cGAS-STING-mediated IFN production. Deficiency in inflammasome signaling enhanced host resistance to DNA virus in vitro and in vivo, and this regulatory role extended to other inflammatory caspases. Thus, inflammasome activation dampens cGAS-dependent signaling, suggesting cross-regulation between intracellular DNA-sensing pathways.
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