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Distinct Roles of Type I and Type III Interferons in Intestinal Immunity to Homologous and Heterologous Rotavirus Infections

Type I (IFN-α/β) and type III (IFN-λ) interferons (IFNs) exert shared antiviral activities through distinct receptors. However, their relative importance for antiviral protection of different organ systems against specific viruses remains to be fully explored. We used mouse strains deficient in type...

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Autores principales: Lin, Jian-Da, Feng, Ningguo, Sen, Adrish, Balan, Murugabaskar, Tseng, Hsiang-Chi, McElrath, Constance, Smirnov, Sergey V., Peng, Jianya, Yasukawa, Linda L., Durbin, Russell K., Durbin, Joan E., Greenberg, Harry B., Kotenko, Sergei V.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4851417/
https://www.ncbi.nlm.nih.gov/pubmed/27128797
http://dx.doi.org/10.1371/journal.ppat.1005600
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author Lin, Jian-Da
Feng, Ningguo
Sen, Adrish
Balan, Murugabaskar
Tseng, Hsiang-Chi
McElrath, Constance
Smirnov, Sergey V.
Peng, Jianya
Yasukawa, Linda L.
Durbin, Russell K.
Durbin, Joan E.
Greenberg, Harry B.
Kotenko, Sergei V.
author_facet Lin, Jian-Da
Feng, Ningguo
Sen, Adrish
Balan, Murugabaskar
Tseng, Hsiang-Chi
McElrath, Constance
Smirnov, Sergey V.
Peng, Jianya
Yasukawa, Linda L.
Durbin, Russell K.
Durbin, Joan E.
Greenberg, Harry B.
Kotenko, Sergei V.
author_sort Lin, Jian-Da
collection PubMed
description Type I (IFN-α/β) and type III (IFN-λ) interferons (IFNs) exert shared antiviral activities through distinct receptors. However, their relative importance for antiviral protection of different organ systems against specific viruses remains to be fully explored. We used mouse strains deficient in type-specific IFN signaling, STAT1 and Rag2 to dissect distinct and overlapping contributions of type I and type III IFNs to protection against homologous murine (EW-RV strain) and heterologous (non-murine) simian (RRV strain) rotavirus infections in suckling mice. Experiments demonstrated that murine EW-RV is insensitive to the action of both types of IFNs, and that timely viral clearance depends upon adaptive immune responses. In contrast, both type I and type III IFNs can control replication of the heterologous simian RRV in the gastrointestinal (GI) tract, and they cooperate to limit extra-intestinal simian RRV replication. Surprisingly, intestinal epithelial cells were sensitive to both IFN types in neonatal mice, although their responsiveness to type I, but not type III IFNs, diminished in adult mice, revealing an unexpected age-dependent change in specific contribution of type I versus type III IFNs to antiviral defenses in the GI tract. Transcriptional analysis revealed that intestinal antiviral responses to RV are triggered through either type of IFN receptor, and are greatly diminished when receptors for both IFN types are lacking. These results also demonstrate a murine host-specific resistance to IFN-mediated antiviral effects by murine EW-RV, but the retention of host efficacy through the cooperative action by type I and type III IFNs in restricting heterologous simian RRV growth and systemic replication in suckling mice. Collectively, our findings revealed a well-orchestrated spatial and temporal tuning of innate antiviral responses in the intestinal tract where two types of IFNs through distinct patterns of their expression and distinct but overlapping sets of target cells coordinately regulate antiviral defenses against heterologous or homologous rotaviruses with substantially different effectiveness.
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spelling pubmed-48514172016-05-07 Distinct Roles of Type I and Type III Interferons in Intestinal Immunity to Homologous and Heterologous Rotavirus Infections Lin, Jian-Da Feng, Ningguo Sen, Adrish Balan, Murugabaskar Tseng, Hsiang-Chi McElrath, Constance Smirnov, Sergey V. Peng, Jianya Yasukawa, Linda L. Durbin, Russell K. Durbin, Joan E. Greenberg, Harry B. Kotenko, Sergei V. PLoS Pathog Research Article Type I (IFN-α/β) and type III (IFN-λ) interferons (IFNs) exert shared antiviral activities through distinct receptors. However, their relative importance for antiviral protection of different organ systems against specific viruses remains to be fully explored. We used mouse strains deficient in type-specific IFN signaling, STAT1 and Rag2 to dissect distinct and overlapping contributions of type I and type III IFNs to protection against homologous murine (EW-RV strain) and heterologous (non-murine) simian (RRV strain) rotavirus infections in suckling mice. Experiments demonstrated that murine EW-RV is insensitive to the action of both types of IFNs, and that timely viral clearance depends upon adaptive immune responses. In contrast, both type I and type III IFNs can control replication of the heterologous simian RRV in the gastrointestinal (GI) tract, and they cooperate to limit extra-intestinal simian RRV replication. Surprisingly, intestinal epithelial cells were sensitive to both IFN types in neonatal mice, although their responsiveness to type I, but not type III IFNs, diminished in adult mice, revealing an unexpected age-dependent change in specific contribution of type I versus type III IFNs to antiviral defenses in the GI tract. Transcriptional analysis revealed that intestinal antiviral responses to RV are triggered through either type of IFN receptor, and are greatly diminished when receptors for both IFN types are lacking. These results also demonstrate a murine host-specific resistance to IFN-mediated antiviral effects by murine EW-RV, but the retention of host efficacy through the cooperative action by type I and type III IFNs in restricting heterologous simian RRV growth and systemic replication in suckling mice. Collectively, our findings revealed a well-orchestrated spatial and temporal tuning of innate antiviral responses in the intestinal tract where two types of IFNs through distinct patterns of their expression and distinct but overlapping sets of target cells coordinately regulate antiviral defenses against heterologous or homologous rotaviruses with substantially different effectiveness. Public Library of Science 2016-04-29 /pmc/articles/PMC4851417/ /pubmed/27128797 http://dx.doi.org/10.1371/journal.ppat.1005600 Text en https://creativecommons.org/publicdomain/zero/1.0/ This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration, which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.
spellingShingle Research Article
Lin, Jian-Da
Feng, Ningguo
Sen, Adrish
Balan, Murugabaskar
Tseng, Hsiang-Chi
McElrath, Constance
Smirnov, Sergey V.
Peng, Jianya
Yasukawa, Linda L.
Durbin, Russell K.
Durbin, Joan E.
Greenberg, Harry B.
Kotenko, Sergei V.
Distinct Roles of Type I and Type III Interferons in Intestinal Immunity to Homologous and Heterologous Rotavirus Infections
title Distinct Roles of Type I and Type III Interferons in Intestinal Immunity to Homologous and Heterologous Rotavirus Infections
title_full Distinct Roles of Type I and Type III Interferons in Intestinal Immunity to Homologous and Heterologous Rotavirus Infections
title_fullStr Distinct Roles of Type I and Type III Interferons in Intestinal Immunity to Homologous and Heterologous Rotavirus Infections
title_full_unstemmed Distinct Roles of Type I and Type III Interferons in Intestinal Immunity to Homologous and Heterologous Rotavirus Infections
title_short Distinct Roles of Type I and Type III Interferons in Intestinal Immunity to Homologous and Heterologous Rotavirus Infections
title_sort distinct roles of type i and type iii interferons in intestinal immunity to homologous and heterologous rotavirus infections
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4851417/
https://www.ncbi.nlm.nih.gov/pubmed/27128797
http://dx.doi.org/10.1371/journal.ppat.1005600
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