Natural Secretory Immunoglobulins Promote Enteric Viral Infections.

Détails

ID Serval
serval:BIB_17273F3FE605
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Natural Secretory Immunoglobulins Promote Enteric Viral Infections.
Périodique
Journal of virology
Auteur(s)
Turula H., Bragazzi Cunha J., Mainou B.A., Ramakrishnan S.K., Wilke C.A., Gonzalez-Hernandez M.B., Pry A., Fava J., Bassis C.M., Edelman J., Shah Y.M., Corthesy B., Moore B.B., Wobus C.E.
ISSN
1098-5514 (Electronic)
ISSN-L
0022-538X
Statut éditorial
Publié
Date de publication
01/12/2018
Peer-reviewed
Oui
Volume
92
Numéro
23
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Résumé
Noroviruses are enteric pathogens causing significant morbidity, mortality, and economic losses worldwide. Secretory immunoglobulins (sIg) are a first line of mucosal defense against enteric pathogens. They are secreted into the intestinal lumen via the polymeric immunoglobulin receptor (pIgR), where they bind to antigens. However, whether natural sIg protect against norovirus infection remains unknown. To determine if natural sIg alter murine norovirus (MNV) pathogenesis, we infected pIgR knockout (KO) mice, which lack sIg in mucosal secretions. Acute MNV infection was significantly reduced in pIgR KO mice compared to controls, despite increased MNV target cells in the Peyer's patch. Natural sIg did not alter MNV binding to the follicle-associated epithelium (FAE) or crossing of the FAE into the lymphoid follicle. Instead, naive pIgR KO mice had enhanced levels of the antiviral inflammatory molecules interferon gamma (IFN-γ) and inducible nitric oxide synthase (iNOS) in the ileum compared to controls. Strikingly, depletion of the intestinal microbiota in pIgR KO and control mice resulted in comparable IFN-γ and iNOS levels, as well as MNV infectious titers. IFN-γ treatment of wild-type (WT) mice and neutralization of IFN-γ in pIgR KO mice modulated MNV titers, implicating the antiviral cytokine in the phenotype. Reduced gastrointestinal infection in pIgR KO mice was also observed with another enteric virus, reovirus. Collectively, our findings suggest that natural sIg are not protective during enteric virus infection, but rather, that sIg promote enteric viral infection through alterations in microbial immune responses.IMPORTANCE Enteric virus, such as norovirus, infections cause significant morbidity and mortality worldwide. However, direct antiviral infection prevention strategies are limited. Blocking host entry and initiation of infection provides an established avenue for intervention. Here, we investigated the role of the polymeric immunoglobulin receptor (pIgR)-secretory immunoglobulin (sIg) cycle during enteric virus infections. The innate immune functions of sIg (agglutination, immune exclusion, neutralization, and expulsion) were not required during control of acute murine norovirus (MNV) infection. Instead, lack of pIgR resulted in increased IFN-γ levels, which contributed to reduced MNV titers. Another enteric virus, reovirus, also showed decreased infection in pIgR KO mice. Collectively, our data point to a model in which sIg-mediated microbial sensing promotes norovirus and reovirus infection. These data provide the first evidence of the proviral role of natural sIg during enteric virus infections and provide another example of how intestinal bacterial communities indirectly influence MNV pathogenesis.
Mots-clé
Animals, Caliciviridae Infections/immunology, Caliciviridae Infections/metabolism, Caliciviridae Infections/virology, Gastrointestinal Tract/immunology, Gastrointestinal Tract/virology, Immunoglobulins/metabolism, Interferon-gamma/metabolism, Mice, Mice, Inbred C57BL, Mice, Knockout, Nitric Oxide Synthase Type II/metabolism, Norovirus/immunology, Receptors, Polymeric Immunoglobulin/physiology, Reoviridae/immunology, Reoviridae Infections/immunology, Reoviridae Infections/metabolism, Reoviridae Infections/virology, Virus Replication/immunology, RNA virus, enteric viruses, gastrointestinal infection, pathogenesis
Pubmed
Web of science
Open Access
Oui
Création de la notice
29/10/2018 11:12
Dernière modification de la notice
22/10/2019 5:11
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