title: Enteric Viruses Ameliorate Gut Inflammation via Toll-like Receptor 3 and Toll-like Receptor 7-Mediated Interferon-β Production.
abstract: 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.
authors.affiliation: Mucosal Immunology Laboratory, Department of Convergence Medicine, University of Ulsan College of Medicine/Asan Medical Center, Seoul 05505, Korea.
authors.forename: Jin-Young
authors.initials: JY
authors.lastname: Yang
authors.affiliation: Department of Life and Nanopharmaceutical Sciences and Department of Biology, Kyung Hee University, Seoul 02447, Korea.
authors.forename: Min-Soo
authors.initials: MS
authors.lastname: Kim
authors.affiliation: Mucosal Immunology Laboratory, Department of Convergence Medicine, University of Ulsan College of Medicine/Asan Medical Center, Seoul 05505, Korea.
authors.forename: Eugene
authors.initials: E
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul 03722l, Korea.
authors.forename: Jae Hee
authors.initials: JH
authors.lastname: Cheon
authors.affiliation: Mucosal Immunology Laboratory, Department of Convergence Medicine, University of Ulsan College of Medicine/Asan Medical Center, Seoul 05505, Korea.
authors.forename: Yong-Soo
authors.initials: YS
authors.lastname: Lee
authors.affiliation: Mucosal Immunology Laboratory, Department of Convergence Medicine, University of Ulsan College of Medicine/Asan Medical Center, Seoul 05505, Korea.
authors.forename: Yeji
authors.initials: Y
authors.lastname: Kim
authors.affiliation: Mucosal Immunology Laboratory, Department of Convergence Medicine, University of Ulsan College of Medicine/Asan Medical Center, Seoul 05505, Korea.
authors.forename: Su-Hyun
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Department of Medicine, Wide River Institute of Immunology, Seoul National University College of Medicine, Seoul 03080, Korea.
authors.forename: Sang-Uk
authors.initials: SU
authors.lastname: Seo
authors.affiliation: Department of Medical Biotechnology, College of Biomedical Science, Kangwon National University, Chuncheon 24341, Korea.
authors.forename: Seung-Ho
authors.initials: SH
authors.lastname: Shin
authors.affiliation: Department of Medical Biotechnology, College of Biomedical Science, Kangwon National University, Chuncheon 24341, Korea.
authors.forename: Sun Shim
authors.initials: SS
authors.lastname: Choi
authors.affiliation: Laboratory of Pathology (BK21 Plus Program), College of Veterinary Medicine, Chonbuk National University, Iksan 54596, Korea.
authors.forename: Bumseok
authors.initials: B
authors.lastname: Kim
authors.affiliation: Laboratory of Microbiology, College of Pharmacy, Ajou University, Suwon 16499, Korea.
authors.forename: Sun-Young
authors.initials: SY
authors.lastname: Chang
authors.affiliation: Laboratory of Microbiology and Immunology, College of Pharmacy, Kangwon National University, Chuncheon 24341, Korea.
authors.forename: Hyun-Jeong
authors.initials: HJ
authors.lastname: Ko
authors.affiliation: Department of Life and Nanopharmaceutical Sciences and Department of Biology, Kyung Hee University, Seoul 02447, Korea. Electronic address: baejw@khu.ac.kr.
authors.forename: Jin-Woo
authors.initials: JW
authors.lastname: Bae
authors.affiliation: Mucosal Immunology Laboratory, Department of Convergence Medicine, University of Ulsan College of Medicine/Asan Medical Center, Seoul 05505, Korea. Electronic address: mnkweon@amc.seoul.kr.
authors.forename: Mi-Na
authors.initials: MN
authors.lastname: Kweon
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology; D003092:Colitis / Q000139:chemically induced / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology; D016264:Dextran Sulfate; D000069196:Gastrointestinal Microbiome; D041981:Gastrointestinal Tract / Q000276:immunology / Q000821:virology*; D006801:Humans; D007249:Inflammation / Q000276:immunology; D016899:Interferon-beta / Q000096:biosynthesis / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D012336:RNA, Ribosomal, 16S / Q000235:genetics; D012401:Rotavirus / Q000276:immunology*; D051196:Toll-Like Receptor 3 / Q000235:genetics / Q000276:immunology*; D051199:Toll-Like Receptor 7 / Q000235:genetics / Q000276:immunology*
chemical_list: D000998:Antiviral Agents; D008562:Membrane Glycoproteins; D012336:RNA, Ribosomal, 16S; C519703:TLR3 protein, mouse; C477038:Tlr7 protein, mouse; D051196:Toll-Like Receptor 3; D051199:Toll-Like Receptor 7; D016899:Interferon-beta; D016264:Dextran Sulfate