Commensal Microbiota Modulation of Natural Resistance to Virus Infection

被引：213

作者：

Stefan, Kailyn L. ^{[1
,4
]}

Kim, Myoungjoo, V ^{[2
,5
]}

Iwasaki, Akiko ^{[2
,3
]}

Kasper, Dennis L. ^{[1
]}

机构：

[1] Harvard Med Sch, Blavatn Inst, Dept Immunol, Boston, MA 02115 USA

[2] Yale Sch Med, Dept Immunobiol, New Haven, CT 06510 USA

[3] Howard Hughes Med Inst, Chevy Chase, Chevy Chase, MD 20815 USA

[4] SQZ Biotechnol, Watertown, MA 02472 USA

[5] Moderna, Cambridge, MA 02139 USA

来源：

CELL | 2020年 / 183卷 / 05期

基金：

美国国家卫生研究院;

关键词：

Bacteroides; dendritic cell; immune modulation; microbiome; type I interferon; virus infection;

D O I：

10.1016/j.cell.2020.10.047

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Interferon (IFN)-Is are crucial mediators of antiviral immunity and homeostatic immune system regulation. However, the source of IFN-I signaling under homeostatic conditions is unclear. We discovered that commensal microbes regulate the IFN-I response through induction of IFN-beta by colonic DCs. Moreover, the mechanism by which a specific commensal microbe induces IFN-beta was identified. Outer membrane (OM)-associated glycolipids of gut commensal microbes belonging to the Bacteroidetes phylum induce expression of IFN-beta. Using Bacteroides fragilis and its OM-associated polysaccharide A, we determined that IFN-beta expression was induced via TLR4-TRIF signaling. Antiviral activity of this purified microbial molecule against infection with either vesicular stomatitis virus (VSV) or influenza was demonstrated to be dependent on the induction of IFN-beta. In a murine VSV infection model, commensal-induced IFN-beta regulated natural resistance to virus infection. Due to the physiological importance of IFN-beta, discovery of an IFN-beta-inducing microbial molecule represents a potential approach for the treatment of some human diseases.

引用

页码：1312 / +

页数：23

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