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The gut microbiota prime systemic antiviral immunity via the cGAS-STING-IFN-I axis
Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.ORCID iD: 0000-0001-6898-0170
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2022 (English)In: Immunity, ISSN 1074-7613, E-ISSN 1097-4180, Vol. 55, no 5, p. 847-861, e1-e10Article in journal (Refereed) Published
Abstract [en]

The microbiota are vital for immune homeostasis and provide a competitive barrier to bacterial and fungal pathogens. Here, we investigated how gut commensals modulate systemic immunity and response to viral infection. Antibiotic suppression of the gut microbiota reduced systemic tonic type I interferon (IFN-I) and antiviral priming. The microbiota-driven tonic IFN-I-response was dependent on cGAS-STING but not on TLR signaling or direct host-bacteria interactions. Instead, membrane vesicles (MVs) from extracellular bacteria activated the cGAS-STING-IFN-I axis by delivering bacterial DNA into distal host cells. DNA-containing MVs from the gut microbiota were found in circulation and promoted the clearance of both DNA (herpes simplex virus type 1) and RNA (vesicular stomatitis virus) viruses in a cGAS-dependent manner. In summary, this study establishes an important role for the microbiota in peripheral cGAS-STING activation, which promotes host resistance to systemic viral infections. Moreover, it uncovers an underappreciated risk of antibiotic use during viral infections.

Place, publisher, year, edition, pages
2022. Vol. 55, no 5, p. 847-861, e1-e10
Keywords [en]
innate immunity, pattern recognition receptors, microbiota, bacterial membrane vesicles, interferons, cGAS, STING, virus, infections
National Category
Immunology in the medical area
Identifiers
URN: urn:nbn:se:su:diva-204891DOI: 10.1016/j.immuni.2022.04.006ISI: 000802171100010PubMedID: 35545033Scopus ID: 2-s2.0-85129773156OAI: oai:DiVA.org:su-204891DiVA, id: diva2:1661986
Available from: 2022-05-30 Created: 2022-05-30 Last updated: 2022-10-25Bibliographically approved

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Swacha, PatrycjaAung, Kyaw MinJiang, HuiGekara, Nelson O.

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