Interleukin-1β Induces mtDNA Release to Activate Innate Immune Signaling via cGAS-STING

被引：309

作者：

Aarreberg, Lauren D. ^{[1
]}

Esser-Nobis, Katharina ^{[1
]}

Driscoll, Connor ^{[1
]}

Shuvarikov, Andrey ^{[1
]}

Roby, Justin A. ^{[1
]}

Gale, Michael, Jr. ^{[1
]}

机构：

[1] Univ Washington, Sch Med, Dept Immunol, Ctr Innate Immun & Immune Dis, Seattle, WA 98109 USA

来源：

MOLECULAR CELL | 2019年 / 74卷 / 04期

关键词：

INTERFERON REGULATORY FACTOR-3; GMP-AMP SYNTHASE; PATTERN-RECOGNITION; I INTERFERONS; CELL-DEATH; IKK-I; IFN; INDUCTION; PHOSPHORYLATION; TRANSCRIPTION;

D O I：

10.1016/j.molcel.2019.02.038

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

Interleukin-1 beta (IL-1 beta) is a pleiotropic mediator of inflammation and is produced in response to a wide range of stimuli. During infection, IL-1 beta production occurs in parallel with the onset of innate antimicrobial defenses, but the contribution of IL-1 beta signaling to cell-intrinsic immunity is not defined. Here, we report that exogenous IL-1 beta induces interferon regulatory factor 3 (IRF3) activation in human myeloid, fibroblast, and epithelial cells. IRF3 activation by IL-1 beta is dependent upon the DNA-sensing pathway adaptor, stimulator of interferon genes (STING), through the recognition of cytosolic mtDNA by cyclic guanosine monophosphate (GMP)-AMP synthase (cGAS). IL-1 beta treatment results in interferon (IFN) production and activation of IFN signaling to direct a potent innate immune response that restricts dengue virus infection. This study identifies a new function for IL-1 beta in the onset or enhancement of cell-intrinsic immunity, with important implications for cGAS-STING in integrating inflammatory and microbial cues for host defense.

引用

页码：801 / +

页数：21

共 57 条

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Interleukin-1β Signaling in Dendritic Cells Induces Antiviral Interferon Responses [J].