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

Immunity. 2016 Apr 19;44(4):889-900. doi: 10.1016/j.immuni.2016.03.009. Epub 2016 Apr 12.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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*


  • Antiviral Agents
  • Membrane Glycoproteins
  • RNA, Ribosomal, 16S
  • TLR3 protein, mouse
  • Tlr7 protein, mouse
  • Toll-Like Receptor 3
  • Toll-Like Receptor 7
  • Interferon-beta
  • Dextran Sulfate