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Pivotal roles of cGAS-cGAMP signaling in antiviral defense and immune adjuvant effects.

ABSTRACT: 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.

SUBMITTER: Li XD

PROVIDER: S-EPMC3863637 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature

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Pivotal roles of cGAS-cGAMP signaling in antiviral defense and immune adjuvant effects.

Li Xiao-Dong XD Wu Jiaxi J Gao Daxing D Wang Hua H Sun Lijun L Chen Zhijian J ZJ

Science (New York, N.Y.) 20130829 6152

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 ...[more]

PMID: 23989956

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