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

被引：294

作者：

Erttmann, Saskia F. ^{[1
]}

Swacha, Patrycja ^{[2
]}

Aung, Kyaw Min ^{[2
]}

Brindefalk, Bjorn ^{[3
]}

Jiang, Hui ^{[2
]}

Hartova, Anetta ^{[4
,5
]}

Uhlin, Bernt Eric ^{[1
]}

Wai, Sun N. ^{[1
]}

Gekara, Nelson O. ^{[1
,2
]}

机构：

[1] Umea Univ, Dept Mol Biol, Umea Ctr Microbial Res UCMR, Lab Mol Infect Med Sweden MIMS, S-90187 Umea, Sweden

[2] Stockholm Univ, Wenner Gren Inst, Dept Mol Biosci, S-10691 Stockholm, Sweden

[3] Swedish Def Res Agcy, CBRN Def & Secur, Umea, Sweden

[4] Univ Gothenburg, Sahlgrenska Acad Fac Sci, Inst Biomed, Dept Microbiol & Immunol, Gothenburg, Sweden

[5] Univ Gothenburg, Wallenberg Ctr Mol & Translat Med, Gothenburg, Sweden

来源：

IMMUNITY | 2022年 / 55卷 / 05期

基金：

瑞典研究理事会;

关键词：

CYTOSOLIC DNA SENSOR; TOLL-LIKE RECEPTORS; COMMENSAL MICROBIOTA; INNATE; INFLUENZA; INFECTION; RESPONSES; BACTERIA; GENES; LIPOPOLYSACCHARIDE;

D O I：

10.1016/j.immuni.2022.04.006

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

071005 [微生物学]; 100108 [医学免疫学];

摘要：

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.

引用

页码：847 / +

页数：26

共 67 条

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