| Title | Inflammasome Activation Triggers Caspase-1-Mediated Cleavage of cGAS to Regulate Responses to DNA Virus Infection |
| Authors | Wang, Yutao Ning, Xiaohan Gao, Pengfei Wu, Shuxian Sha, Mengyin Lv, Mengze Zhou, Xiang Gao, Juyi Fang, Run Meng, Guangxun Su, Xiaodong Jiang, Zhengfan |
| Affiliation | Peking Univ, Sch Life Sci, State Key Lab Prot & Plant Gene Res, Beijing 100871, Peoples R China. Peking Univ, Key Lab Cell Proliferat & Differentiat, Minist Educ, Sch Life Sci, Beijing 100871, Peoples R China. Peking Tsinghua Ctr Life Sci, Beijing 100871, Peoples R China. Chinese Acad Sci, Inst Pasteur Shanghai, Key Lab Mol Virol & Immunol, Shanghai 200031, Peoples R China. Peking Univ, Sch Life Sci, State Key Lab Prot & Plant Gene Res, Beijing 100871, Peoples R China. Jiang, ZF (reprint author), Peking Univ, Key Lab Cell Proliferat & Differentiat, Minist Educ, Sch Life Sci, Beijing 100871, Peoples R China. Jiang, ZF (reprint author), Peking Tsinghua Ctr Life Sci, Beijing 100871, Peoples R China. |
| Keywords | NF-KAPPA-B CYCLIC GMP-AMP PYROPTOTIC CELL-DEATH DOUBLE-STRANDED-RNA I INTERFERON RIG-I CYTOSOLIC DNA ADAPTER PROTEIN HOST-DEFENSE INNATE |
| Issue Date | 2017 |
| Publisher | IMMUNITY |
| Citation | IMMUNITY.2017,46(3),393-404. |
| Abstract | 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 cGASSTING- 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. |
| URI | http://hdl.handle.net/20.500.11897/474529 |
| ISSN | 1074-7613 |
| DOI | 10.1016/j.immuni.2017.02.011 |
| Indexed | SCI(E) |
| Appears in Collections: | 生命科学学院 细胞增殖分化调控机理研究教育部重点实验室 |
