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

Xiao Dong Li, Jiaxi Wu, Daxing Gao, Hua Wang, Lijun Sun, Zhijian J. Chen

Research output: Contribution to journalArticle

371 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1390-1394
Number of pages5
JournalScience
Volume341
Issue number6152
DOIs
StatePublished - 2013

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Antiviral Agents
DNA
DNA Virus Infections
Cytoplasm
CD27 Antigens
Interferon Type I
Human Herpesvirus 1
Infection
Innate Immunity
Dendritic Cells
Autoimmune Diseases
Antibody Formation
Transfection
Fibroblasts
Macrophages
Cytokines
cyclic guanosine monophosphate-adenosine monophosphate

ASJC Scopus subject areas

  • General

Cite this

Pivotal roles of cGAS-cGAMP signaling in antiviral defense and immune adjuvant effects. / Li, Xiao Dong; Wu, Jiaxi; Gao, Daxing; Wang, Hua; Sun, Lijun; Chen, Zhijian J.

In: Science, Vol. 341, No. 6152, 2013, p. 1390-1394.

Research output: Contribution to journalArticle

Li, Xiao Dong ; Wu, Jiaxi ; Gao, Daxing ; Wang, Hua ; Sun, Lijun ; Chen, Zhijian J. / Pivotal roles of cGAS-cGAMP signaling in antiviral defense and immune adjuvant effects. In: Science. 2013 ; Vol. 341, No. 6152. pp. 1390-1394.
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