Enteric Viruses Ameliorate Gut Inflammation via Toll-like Receptor 3 and Toll-like Receptor 7-Mediated Interferon-β Production

Metagenomic studies show that diverse resident viruses inhabit the healthy gut; however, little is known about the role of these viruses in the maintenance of gut homeostasis. We found that mice treated with antiviral cocktail displayed more severe dextran sulfate sodium (DSS)-induced colitis compar...

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Bibliographic Details
Published in:Immunity (Cambridge, Mass.) Mass.), 2016-04, Vol.44 (4), p.889-900
Main Authors: Yang, Jin-Young, Kim, Min-Soo, Kim, Eugene, Cheon, Jae Hee, Lee, Yong-Soo, Kim, Yeji, Lee, Su-Hyun, Seo, Sang-Uk, Shin, Seung-Ho, Choi, Sun Shim, Kim, Bumseok, Chang, Sun-Young, Ko, Hyun-Jeong, Bae, Jin-Woo, Kweon, Mi-Na
Format: Article
Language:English
Subjects:
Animals
Antiviral Agents - pharmacology
Colitis - chemically induced
Colitis - immunology
Dendritic Cells - immunology
Dextran Sulfate
Gastrointestinal Microbiome
Gastrointestinal Tract - immunology
Gastrointestinal Tract - virology
Humans
Inflammation - immunology
Interferon-beta - biosynthesis
Interferon-beta - immunology
Membrane Glycoproteins - genetics
Membrane Glycoproteins - immunology
Mice
Mice, Inbred BALB C
Mice, Knockout
RNA, Ribosomal, 16S - genetics
Rotavirus - immunology
Toll-Like Receptor 3 - genetics
Toll-Like Receptor 3 - immunology
Toll-Like Receptor 7 - genetics
Toll-Like Receptor 7 - immunology
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Summary:Metagenomic studies show that diverse resident viruses inhabit the healthy gut; however, little is known about the role of these viruses in the maintenance of gut homeostasis. We found that mice treated with antiviral cocktail displayed more severe dextran sulfate sodium (DSS)-induced colitis compared with untreated mice. DSS-induced colitis was associated with altered enteric viral abundance and composition. When wild-type mice were reconstituted with Toll-like receptor 3 (TLR3) or TLR7 agonists or inactivated rotavirus, colitis symptoms were significantly ameliorated. Mice deficient in both TLR3 and TLR7 were more susceptible to DSS-induced experimental colitis. In humans, combined TLR3 and TLR7 genetic variations significantly influenced the severity of ulcerative colitis. Plasmacytoid dendritic cells isolated from inflamed mouse colon produced interferon-β in a TLR3 and TLR7-dependent manner. These results imply that recognition of resident viruses by TLR3 and TLR7 is required for protective immunity during gut inflammation. [Display omitted] •Pre-treatment with an antiviral cocktail results in severe colitis•Treatment with TLR3+7 agonists and inactivated rotavirus ameliorates colitis•Tlr3−/−Tlr7−/− mice are more susceptible to colitis•TLR3+7 agonists stimulate IFN-β secretion by pDCs from inflamed colon The role of gut resident viruses in the maintenance of homeostasis is unclear. Kweon and colleagues show the sensing of gut viruses by TLR3 or TLR7 enhances the production of interferon-β that dampens inflammation.
ISSN:1074-7613
1097-4180
DOI:10.1016/j.immuni.2016.03.009