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Interleukin-1β Induces mtDNA Release to Activate Innate Immune Signaling via cGAS-STING
Open accessAbstract
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.
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“mtDNA or mtRNA released into the cytosol via BAX–BAK macropores can activate nucleic acid sensors in the cytosol145 independently of cell death130,146,147, ultimately leading to the production of type I interferon”
From The role of mitochondria in rheumatic diseases (2022) · cites this paper as [146]
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“IL-1β, a major SASP factor, can induce mtDNA release with subsequent activation of pro-inflammatory pathways (Aarreberg et al., 2019).”
From Cytoplasmic DNA: sources, sensing, and role in aging and disease (2021) · cites this paper as Aarreberg et al., 2019
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Metadata
- Authors
- Aarreberg, L. D., Esser-Nobis, K., Driscoll, C., Shuvarikov, A., Roby, J. A., & Gale, M.
- Affiliations
- University of Washington (US)
- Corresponding author
- Gale, Michael
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2019-05
- Volume
- 74
- Issue
- 4
- Pages
- 801-815.e6
- ISSN
- 1097-2765 (ISSN-L)
- PMC
- PMC6596306
- OpenAlex
- W2934093192
- Cited by
- 328
- References
- 58
- Citations by year
- 2026: 39 · 2025: 37 · 2024: 65 · 2023: 60 · 2022: 41 · 2021: 47 · 2020: 31 · 2019: 8
- FWCI
- 12.66
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Molecular Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Charles Sturt University Research Output (CRO) (submittedVersion, cc-by-nc-nd)
- Funders
- NIH (AI27463, AI118916, AI100625, AI104002, AI083019, T32AI106677-03)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Keywords
- IL-1β, mitochondrial DNA release, cGAS-STING pathway, IRF3 activation, interferon signaling, innate immunity, dengue virus, cell-intrinsic immunity, DNA sensing, infection and inflammation
- MeSH terms
- STING Protein, Cyclic Guanosine Monophosphate-Adenosine Monophosphate Synthase, Dengue, Dengue Virus, DNA, Mitochondrial, Cyclic GMP, Humans, Immunity, Innate, Inflammation, Interferons, Membrane Proteins, Nucleotidyltransferases, Signal Transduction, Myeloid Cells, Interferon Regulatory Factor-3, Interleukin-1beta, Host-Pathogen Interactions
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