The gut microbiota prime systemic antiviral immunity via the cGAS-STING-IFN-I axis.

Abstract

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.

• Authors: Saskia F Erttmann, Patrycja Swacha, Kyaw Min Aung, Björn Brindefalk, Hui Jiang, Anetta Härtlova, Bernt Eric Uhlin, Sun N Wai, Nelson O Gekara
• Journal: Immunity (Immunity) Vol. 55 Issue 5 Pg. 847-861.e10 (05 10 2022) ISSN: 1097-4180 [Electronic] United States
• PMID: 35545033 (Publication Type: Journal Article)
• Copyright: Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.

Chemical References

• Anti-Bacterial Agents
• Antiviral Agents
• Interferon Type I
• Membrane Proteins
• STING1 protein, human
• Nucleotidyltransferases
• cGAS protein, human

Topics

• Anti-Bacterial Agents
• Antiviral Agents
• Gastrointestinal Microbiome
• Herpesvirus 1, Human
• Humans
• Immunity, Innate
• Interferon Type I
• Membrane Proteins (genetics)
• Nucleotidyltransferases (genetics)
• Virus Diseases