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

Yang et al. Immunity 44: 889-900, 2016

Speaker: Wei-Kuan Sung (宋惟寬)                              Time: 13:00~14:00 March 8, 2017

Commentator: Dr. Shun-Hua Chen (陳舜華老師)       Place: Room 601

Abstract:

Inflammatory bowel disease (IBD), including Crohn’s disease and ulcerative colitis, is a common, chronic disorder that causes abdominal pain, diarrhea, and gastrointestinal bleeding. Treatment of IBD is based on several different approaches relying on aminosalicylates, antibiotics, corticosteroids, and immunomodulatory agents, in addition to the newest biological agents. However, the mechanisms responsible for the initiation and chronicity of intestinal inflammation remain poorly understood^1,2. IBD is believed to result from interactions of immunological, genetic, microbial, and environmental factors that induce gut inflammation. Diverse resident viruses inhabit the healthy gut; however, their roles in the maintenance of gut homeostasis are unclear. In the past, intestinal viruses have been thought to be detrimental or neutral to the host. In this study, the authors investigated whether viruses have a role as resident commensals that elicit innate immune responses under inflammatory conditions. The authors found that mice pretreated with antiviral cocktail exhibited more severe dextran sulfate sodium (DSS)-induced colitis compared with untreated mice, suggesting that commensal viruses play a protective role against the disease. Antiviral agents altered the abundance and composition of gut viral and bacterial communities. Mice treated with Toll-like receptor (TLR) 3+7 agonists attenuated DSS-induced colitis. Furthermore, mice deficient in both TLR3 and TLR7 were more susceptible to DSS-induced colitis compared with their wild-type counterparts. These results suggest that TLR3 and TLR7 signaling pathways contribute to the attenuation of gut inflammation. Moreover, plasmacytoid dendritic cells isolated from inflamed mouse colon produced interferon-β in a TLR3- and TLR7-dependent manner. In human study, the combined mutations of TLR3 and TLR7 genes affected disease severity of patients with ulcerative colitis. Taken together, these results imply that recognition of resident intestinal viruses through TLR3- and TLR7-mediated interferon-β production by plasmacytoid dendritic cells play a protective role in gut inflammation.

References

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2.         Kaser A, Zeissig S and Blumberg RS. Inflammatory bowel disease. Annu. Rev. Immunol. 28: 573-621, 2010.