title: 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.
authors.affiliation: Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9148, USA.
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Li
authors.forename: Jiaxi
authors.initials: J
authors.lastname: Wu
authors.forename: Daxing
authors.initials: D
authors.lastname: Gao
authors.forename: Hua
authors.initials: H
authors.lastname: Wang
authors.forename: Lijun
authors.initials: L
authors.lastname: Sun
authors.forename: Zhijian J
authors.initials: ZJ
authors.lastname: Chen
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D004279:DNA, Viral / Q000235:genetics / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D005347:Fibroblasts / Q000276:immunology; D006561:Herpes Simplex / Q000276:immunology*; D018259:Herpesvirus 1, Human; D050838:Interferon Regulatory Factor-3 / Q000235:genetics; D016899:Interferon-beta / Q000096:biosynthesis* / Q000235:genetics; D008213:Lymphocyte Activation; D008264:Macrophages / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D009713:Nucleotidyltransferases / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology; D014162:Transfection; D000099235:Cyclic Guanosine Monophosphate-Adenosine Monophosphate Synthase
chemical_list: D000914:Antibodies, Viral; D004279:DNA, Viral; D050838:Interferon Regulatory Factor-3; D016899:Interferon-beta; D009713:Nucleotidyltransferases; C494233:Irf3 protein, mouse; C578391:cGAS protein, mouse; D000099235:Cyclic Guanosine Monophosphate-Adenosine Monophosphate Synthase