Interleukin-1β induces mtDNA release to activate innate immune signaling via cGAS-STING

Lauren D Aarreberg, Katharina Esser-Nobis, Connor Driscoll, Andrey Shuvarikov, Justin A Roby, Michael Gale

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112 Citations (Scopus)
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Interleukin-1 beta (IL-1β) is a pleiotropic mediator of inflammation and is produced in response to a wide range of stimuli. During infection, IL-1β production occurs in parallel with the onset of innate antimicrobial defenses, but the contribution of IL-1β signaling to cell-intrinsic immunity is not defined. Here, we report that exogenous IL-1β induces interferon regulatory factor 3 (IRF3) activation in human myeloid, fibroblast, and epithelial cells. IRF3 activation by IL-1β 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-1β 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-1β in the onset or enhancement of cell-intrinsic immunity, with important implications for cGAS-STING in integrating inflammatory and microbial cues for host defense.

Original languageEnglish
Pages (from-to)801-815
Number of pages15
JournalMolecular Cell
Issue number4
Early online date02 Apr 2019
Publication statusPublished - 16 May 2019


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