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CD200 Receptor Restriction of Myeloid Cell Responses Antagonizes Antiviral Immunity and Facilitates Cytomegalovirus Persistence within Mucosal Tissue

CD200 receptor (CD200R) negatively regulates peripheral and mucosal innate immune responses. Viruses, including herpesviruses, have acquired functional CD200 orthologs, implying that viral exploitation of this pathway is evolutionary advantageous. However, the role that CD200R signaling plays during...

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Autores principales: Stack, Gabrielle, Jones, Emma, Marsden, Morgan, Stacey, Maria A., Snelgrove, Robert J., Lacaze, Paul, Jacques, Laura C., Cuff, Simone M., Stanton, Richard J., Gallimore, Awen M., Hussell, Tracy, Wilkinson, Gavin W. G., Ghazal, Peter, Taylor, Philip R., Humphreys, Ian R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4412112/
https://www.ncbi.nlm.nih.gov/pubmed/25654642
http://dx.doi.org/10.1371/journal.ppat.1004641
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author Stack, Gabrielle
Jones, Emma
Marsden, Morgan
Stacey, Maria A.
Snelgrove, Robert J.
Lacaze, Paul
Jacques, Laura C.
Cuff, Simone M.
Stanton, Richard J.
Gallimore, Awen M.
Hussell, Tracy
Wilkinson, Gavin W. G.
Ghazal, Peter
Taylor, Philip R.
Humphreys, Ian R.
author_facet Stack, Gabrielle
Jones, Emma
Marsden, Morgan
Stacey, Maria A.
Snelgrove, Robert J.
Lacaze, Paul
Jacques, Laura C.
Cuff, Simone M.
Stanton, Richard J.
Gallimore, Awen M.
Hussell, Tracy
Wilkinson, Gavin W. G.
Ghazal, Peter
Taylor, Philip R.
Humphreys, Ian R.
author_sort Stack, Gabrielle
collection PubMed
description CD200 receptor (CD200R) negatively regulates peripheral and mucosal innate immune responses. Viruses, including herpesviruses, have acquired functional CD200 orthologs, implying that viral exploitation of this pathway is evolutionary advantageous. However, the role that CD200R signaling plays during herpesvirus infection in vivo requires clarification. Utilizing the murine cytomegalovirus (MCMV) model, we demonstrate that CD200R facilitates virus persistence within mucosal tissue. Specifically, MCMV infection of CD200R-deficient mice (CD200R(-/-)) elicited heightened mucosal virus-specific CD4 T cell responses that restricted virus persistence in the salivary glands. CD200R did not directly inhibit lymphocyte effector function. Instead, CD200R(-/-) mice exhibited enhanced APC accumulation that in the mucosa was a consequence of elevated cellular proliferation. Although MCMV does not encode an obvious CD200 homolog, productive replication in macrophages induced expression of cellular CD200. CD200 from hematopoietic and non-hematopoietic cells contributed independently to suppression of antiviral control in vivo. These results highlight the CD200-CD200R pathway as an important regulator of antiviral immunity during cytomegalovirus infection that is exploited by MCMV to establish chronicity within mucosal tissue.
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spelling pubmed-44121122015-05-07 CD200 Receptor Restriction of Myeloid Cell Responses Antagonizes Antiviral Immunity and Facilitates Cytomegalovirus Persistence within Mucosal Tissue Stack, Gabrielle Jones, Emma Marsden, Morgan Stacey, Maria A. Snelgrove, Robert J. Lacaze, Paul Jacques, Laura C. Cuff, Simone M. Stanton, Richard J. Gallimore, Awen M. Hussell, Tracy Wilkinson, Gavin W. G. Ghazal, Peter Taylor, Philip R. Humphreys, Ian R. PLoS Pathog Research Article CD200 receptor (CD200R) negatively regulates peripheral and mucosal innate immune responses. Viruses, including herpesviruses, have acquired functional CD200 orthologs, implying that viral exploitation of this pathway is evolutionary advantageous. However, the role that CD200R signaling plays during herpesvirus infection in vivo requires clarification. Utilizing the murine cytomegalovirus (MCMV) model, we demonstrate that CD200R facilitates virus persistence within mucosal tissue. Specifically, MCMV infection of CD200R-deficient mice (CD200R(-/-)) elicited heightened mucosal virus-specific CD4 T cell responses that restricted virus persistence in the salivary glands. CD200R did not directly inhibit lymphocyte effector function. Instead, CD200R(-/-) mice exhibited enhanced APC accumulation that in the mucosa was a consequence of elevated cellular proliferation. Although MCMV does not encode an obvious CD200 homolog, productive replication in macrophages induced expression of cellular CD200. CD200 from hematopoietic and non-hematopoietic cells contributed independently to suppression of antiviral control in vivo. These results highlight the CD200-CD200R pathway as an important regulator of antiviral immunity during cytomegalovirus infection that is exploited by MCMV to establish chronicity within mucosal tissue. Public Library of Science 2015-02-05 /pmc/articles/PMC4412112/ /pubmed/25654642 http://dx.doi.org/10.1371/journal.ppat.1004641 Text en © 2015 Stack et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Stack, Gabrielle
Jones, Emma
Marsden, Morgan
Stacey, Maria A.
Snelgrove, Robert J.
Lacaze, Paul
Jacques, Laura C.
Cuff, Simone M.
Stanton, Richard J.
Gallimore, Awen M.
Hussell, Tracy
Wilkinson, Gavin W. G.
Ghazal, Peter
Taylor, Philip R.
Humphreys, Ian R.
CD200 Receptor Restriction of Myeloid Cell Responses Antagonizes Antiviral Immunity and Facilitates Cytomegalovirus Persistence within Mucosal Tissue
title CD200 Receptor Restriction of Myeloid Cell Responses Antagonizes Antiviral Immunity and Facilitates Cytomegalovirus Persistence within Mucosal Tissue
title_full CD200 Receptor Restriction of Myeloid Cell Responses Antagonizes Antiviral Immunity and Facilitates Cytomegalovirus Persistence within Mucosal Tissue
title_fullStr CD200 Receptor Restriction of Myeloid Cell Responses Antagonizes Antiviral Immunity and Facilitates Cytomegalovirus Persistence within Mucosal Tissue
title_full_unstemmed CD200 Receptor Restriction of Myeloid Cell Responses Antagonizes Antiviral Immunity and Facilitates Cytomegalovirus Persistence within Mucosal Tissue
title_short CD200 Receptor Restriction of Myeloid Cell Responses Antagonizes Antiviral Immunity and Facilitates Cytomegalovirus Persistence within Mucosal Tissue
title_sort cd200 receptor restriction of myeloid cell responses antagonizes antiviral immunity and facilitates cytomegalovirus persistence within mucosal tissue
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4412112/
https://www.ncbi.nlm.nih.gov/pubmed/25654642
http://dx.doi.org/10.1371/journal.ppat.1004641
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