Murine Norovirus Infection Induces TH1 Inflammatory Responses to Dietary Antigens

Romain Bouziat; Scott B Biering; Elaine Kouame; Kishan A Sangani; Soowon Kang; Jordan D Ernest; Mukund Varma; Judy J Brown; Kelly Urbanek; Terence S Dermody; Aylwin Ng; Reinhard Hinterleitner; Seungmin Hwang; Bana Jabri

doi:10.1016/j.chom.2018.10.004

Murine Norovirus Infection Induces T_H1 Inflammatory Responses to Dietary Antigens

Cell Host Microbe. 2018 Nov 14;24(5):677-688.e5. doi: 10.1016/j.chom.2018.10.004. Epub 2018 Nov 1.

Authors

Affiliations

¹ Department of Medicine, University of Chicago, Chicago, IL, USA; Committee on Immunology, University of Chicago, Chicago, IL, USA.
² Committee on Microbiology, University of Chicago, Chicago, IL, USA.
³ Department of Pathology, University of Chicago, Chicago, IL, USA.
⁴ Division of Gastroenterology, Department of Medicine, Gastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA; Broad Institute of MIT and Harvard University, Cambridge, MA, USA.
⁵ Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA.
⁶ Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
⁷ Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
⁸ Committee on Immunology, University of Chicago, Chicago, IL, USA; Committee on Microbiology, University of Chicago, Chicago, IL, USA; Department of Pathology, University of Chicago, Chicago, IL, USA. Electronic address: shwang@bsd.uchicago.edu.
⁹ Department of Medicine, University of Chicago, Chicago, IL, USA; Committee on Immunology, University of Chicago, Chicago, IL, USA; Department of Pathology, University of Chicago, Chicago, IL, USA; Section of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of Chicago, Chicago, IL, USA. Electronic address: bjabri@bsd.uchicago.edu.

Abstract

Intestinal reovirus infection can trigger T helper 1 (T_H1) immunity to dietary antigen, raising the question of whether other viruses can have a similar impact. Here we show that the acute CW3 strain of murine norovirus, but not the persistent CR6 strain, induces T_H1 immunity to dietary antigen. This property of CW3 is dependent on its major capsid protein, a virulence determinant. Transcriptional profiling of mesenteric lymph nodes following infection reveals an immunopathological signature that does not segregate with protective immunity but with loss of oral tolerance, in which interferon regulatory factor 1 is critical. These data show that viral capacity to trigger specific inflammatory pathways at sites where T cell responses to dietary antigens take place interferes with the development of tolerance to an oral antigen. Collectively, these data provide a foundation for the development of therapeutic strategies to prevent T_H1-mediated complex immune disorders triggered by viral infections.

Keywords: IRF1; T helper 1; T(H)1; celiac disease; inflammation; interferon regulatory factor 1; major capsid protein; norovirus; oral tolerance; reovirus.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Administration, Oral
Animals
Caliciviridae Infections / immunology*
Caliciviridae Infections / virology
Capsid Proteins / immunology
Celiac Disease / immunology
Diet*
Disease Models, Animal
Female
HEK293 Cells
Humans
Immunity
Inflammation
Interferon Regulatory Factor-1 / immunology
Lymph Nodes
Mice
Mice, Inbred C57BL
Norovirus / immunology*
Norovirus / pathogenicity*
Ovalbumin / administration & dosage
Ovalbumin / immunology*
Th1 Cells / immunology*
Virus Shedding

Substances

Capsid Proteins
Interferon Regulatory Factor-1
Irf1 protein, mouse
Ovalbumin

Abstract

Publication types

MeSH terms

Substances

Grants and funding