Pivotal Roles of cGAS-cGAMP Signaling in Antiviral Defense and Immune Adjuvant Effects

被引：1166

作者：

Li, Xiao-Dong ^{[1
]}

Wu, Jiaxi ^{[1
]}

Gao, Daxing ^{[1
]}

Wang, Hua ^{[1
]}

Sun, Lijun ^{[1
,2
]}

Chen, Zhijian J. ^{[1
,2
]}

机构：

[1] Univ Texas SW Med Ctr Dallas, Dept Mol Biol, Dallas, TX 75390 USA

[2] Univ Texas SW Med Ctr Dallas, Howard Hughes Med Inst, Dallas, TX 75390 USA

来源：

SCIENCE | 2013年 / 341卷 / 6152期

关键词：

CYCLIC GMP-AMP; CYTOSOLIC DNA; RIG-I; INNATE; 2ND-MESSENGER; SENSOR; DINUCLEOTIDE; RECOGNITION;

D O I：

10.1126/science.1244040

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

Invasion of microbial DNA into the cytoplasm of animal cells triggers a cascade of host immune reactions that help clear the infection; however, self DNA in the cytoplasm can cause autoimmune diseases. Biochemical approaches led to the identification of cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) synthase (cGAS) as a cytosolic DNA sensor that triggers innate immune responses. Here, we show that cells from cGAS-deficient (cGas(-/-)) mice, including fibroblasts, macrophages, and dendritic cells, failed to produce type I interferons and other cytokines in response to DNA transfection or DNA virus infection. cGas(-/-) mice were more susceptible to lethal infection with herpes simplex virus 1 (HSV1) than wild-type mice. We also show that cGAMP is an adjuvant that boosts antigen-specific T cell activation and antibody production in mice.

引用

页码：1390 / 1394

页数：5

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