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

Research output: Contribution to journalArticle

25 Citations (Scopus)
1 Downloads (Pure)

Abstract

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
Volume74
Issue number4
Early online date02 Apr 2019
DOIs
Publication statusPublished - 16 May 2019

Fingerprint Dive into the research topics of 'Interleukin-1β Induces mtDNA Release to Activate Innate Immune Signaling via cGAS-STING'. Together they form a unique fingerprint.

  • Cite this