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 ORCID: https://orcid.org/0000-0002-0546-3579, Stanton, Richard J. ORCID: https://orcid.org/0000-0002-6799-1182, Gallimore, Awen M. ORCID: https://orcid.org/0000-0001-6675-7004, Hussell, Tracy, Wilkinson, Gavin W. G. ORCID: https://orcid.org/0000-0002-5623-0126, Ghazal, Peter ORCID: https://orcid.org/0000-0003-0035-2228, Taylor, Philip R. ORCID: https://orcid.org/0000-0003-0163-1421 and Humphreys, Ian R. ORCID: https://orcid.org/0000-0002-9512-5337 2015. CD200 receptor restriction of myeloid cell responses antagonizes antiviral immunity and facilitates cytomegalovirus persistence within mucosal tissue. PLoS Pathogens 11 (2) , e1004641. 10.1371/journal.ppat.1004641

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Abstract

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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine Systems Immunity Research Institute (SIURI)
Subjects:	R Medicine > R Medicine (General)
Additional Information:	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 credited.
Publisher:	Public Library of Science
ISSN:	1553-7366
Funders:	Wellcome Trust
Date of First Compliant Deposit:	30 March 2016
Date of Acceptance:	22 December 2014
Last Modified:	06 Nov 2024 22:44
URI:	https://orca.cardiff.ac.uk/id/eprint/71956

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