肉豆蔻酸
刺
肉豆蔻酰化
自噬
干扰素基因刺激剂
干扰素
细胞生物学
免疫系统
生物
先天免疫系统
病毒学
免疫学
生物化学
脂肪酸
磷酸化
棕榈酸
细胞凋亡
工程类
航空航天工程
作者
Mutian Jia,Yuanyuan Wang,Jie Wang,Danhui Qin,Mengge Wang,Li Chai,Yue Fu,Chenyang Zhao,Chengjiang Gao,Jihui Jia,Wei Zhao
标识
DOI:10.1038/s41467-023-36332-3
摘要
Stimulator of interferon gene (STING)-triggered autophagy is crucial for the host to eliminate invading pathogens and serves as a self-limiting mechanism of STING-induced interferon (IFN) responses. Thus, the mechanisms that ensure the beneficial effects of STING activation are of particular importance. Herein, we show that myristic acid, a type of long-chain saturated fatty acid (SFA), specifically attenuates cGAS-STING-induced IFN responses in macrophages, while enhancing STING-dependent autophagy. Myristic acid inhibits HSV-1 infection-induced innate antiviral immune responses and promotes HSV-1 replication in mice in vivo. Mechanistically, myristic acid enhances N-myristoylation of ARF1, a master regulator that controls STING membrane trafficking. Consequently, myristic acid facilitates STING activation-triggered autophagy degradation of the STING complex. Thus, our work identifies myristic acid as a metabolic checkpoint that contributes to immune homeostasis by balancing STING-dependent autophagy and IFN responses. This suggests that myristic acid and N-myristoylation are promising targets for the treatment of diseases caused by aberrant STING activation.
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