| Title | Apoptotic Caspases Suppress Type I Interferon Production via the Cleavage of cGAS, MAVS, and IRF3 |
| Authors | Ning, Xiaohan Wang, Yutao Jing, Miao Sha, Mengyin Lv, Mengze Gao, Pengfei Zhang, Rui Huang, Xiaojun Feng, Ji-Ming Jiang, Zhengfan |
| Affiliation | Peking Univ, Sch Life Sci, Minist Educ, Key Lab Cell Proliferat & Differentiat, Beijing 100871, Peoples R China Peking Tsinghua Ctr Life Sci, Beijing 100871, Peoples R China Peking Univ, Collaborat Innovat Ctr Hematol, Beijing Key Lab Hematopoiet Stem Cell Transplanta, Inst Hematol, Beijing 100044, Peoples R China Louisiana State Univ, Sch Vet Med, Dept Comparat Biomed Sci, Baton Rouge, LA 70803 USA |
| Issue Date | 2019 |
| Publisher | MOLECULAR CELL |
| Abstract | Viral infection triggers host defenses through pattern-recognition receptor-mediated cytokine production, inflammasome activation, and apoptosis of the infected cells. Inflammasome-activated caspases are known to cleave cyclic GMP-AMP synthase (cGAS). Here, we found that apoptotic caspases are critically involved in regulating both DNA and RNA virus-triggered host defenses, in which activated caspase-3 cleaved cGAS, MAVS, and IRF3 to prevent cytokine overproduction. Caspase-3 was exclusively required in human cells, whereas caspase-7 was involved only in murine cells to inactivate cGAS, reflecting distinct regulatory mechanisms in different species. Caspase-mediated cGAS cleavage was enhanced in the presence of dsDNA. Alternative MAVS cleavage sites were used to ensure the inactivation of this critical protein. Elevated type I IFNs were detected in caspase-3-deficient cells without any infection. Casp3(-/-) mice consistently showed increased resistance to viral infection and experimental autoimmune encephalomyelitis. Our results demonstrate that apoptotic caspases control innate immunity and maintain immune homeostasis against viral infection. |
| URI | http://hdl.handle.net/20.500.11897/549209 |
| ISSN | 1097-2765 |
| DOI | 10.1016/j.molcel.2019.02.013 |
| 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 医学部待认领 |
