| Title | Manganese Increases the Sensitivity of the cGAS-STING Pathway for Double-Stranded DNA and Is Required for the Host Defense against DNA Viruses |
| Authors | Wang, Chenguang Guan, Yukun Lv, Mengze Zhang, Rui Guo, Zhaoying Wei, Xiaoming Du, Xiaoxia Yang, Jing Li, Tong Wan, Yi Su, Xiaodong Huang, Xiaojun Jiang, Zhengfan |
| Affiliation | Peking Univ, Sch Life Sci, Key Lab Cell Proliferat & Differentiat, Minist Educ, Beijing 100871, Peoples R China. Peking Univ, Sch Life Sci, State Key Lab Prot & Plant Gene Res, Beijing 100871, Peoples R China. Peking Univ, Peking Tsinghua Ctr Life Sci, Beijing 100871, Peoples R China. Peking Univ, Coll Urban & Environm Sci, Lab Earth Surface Proc, Beijing 100871, Peoples R China. Peking Univ, Peoples Hosp, Inst Hematol,Collaborat Innovat Ctr Hematol, Beijing Key Lab Hematopoiet Stem Cell Transplanta, Beijing 100044, Peoples R China. Peking Univ, Sch Life Sci, Key Lab Cell Proliferat & Differentiat, Minist Educ, Beijing 100871, Peoples R China. Jiang, ZF (reprint author), Peking Univ, Sch Life Sci, State Key Lab Prot & Plant Gene Res, Beijing 100871, Peoples R China. Jiang, ZF (reprint author), Peking Univ, Peking Tsinghua Ctr Life Sci, Beijing 100871, Peoples R China. |
| Keywords | Innate immunity,Manganese,STING,cGAS,interferons,virus infection CYCLIC GMP-AMP CYTOSOLIC DNA MITOCHONDRIAL-DNA IMMUNE-SYSTEM RAT-LIVER VITAMIN-D IN-VITRO CELLS 2ND-MESSENGER SYNTHASE |
| Issue Date | 2018 |
| Publisher | IMMUNITY |
| Citation | IMMUNITY. 2018, 48(4), 675-+. |
| Abstract | Manganese (Mn) is essential for many physiological processes, but its functions in innate immunity remain undefined. Here, we found that Mn2+ was required for the host defense against DNA viruses by increasing the sensitivity of the DNA sensor cGAS and its downstream adaptor protein STING. Mn2+ was released from membrane-enclosed organelles upon viral infection and accumulated in the cytosol where it bound directly to cGAS. Mn2+ enhanced the sensitivity of cGAS to double-stranded DNA (dsDNA) and its enzymatic activity, enabling cGAS to produce secondary messenger cGAMP in the presence of low concentrations of dsDNA that would otherwise be non-stimulatory. Mn2+ also enhanced STING activity by augmenting cGAMP-STING binding affinity. Mn-deficient mice showed diminished cytokine production and were more vulnerable to DNA viruses, and Mn-deficient STING-deficient mice showed no increased susceptibility. These findings indicate that Mn is critically involved and required for the host defense against DNA viruses. |
| URI | http://hdl.handle.net/20.500.11897/513066 |
| ISSN | 1074-7613 |
| DOI | 10.1016/j.immuni.2018.03.017 |
| Indexed | SCI(E) PubMed Medline |
| 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 城市与环境学院 地表过程分析与模拟教育部重点实验室 人民医院 |
