title: CD200 receptor restriction of myeloid cell responses antagonizes antiviral immunity and facilitates cytomegalovirus persistence within mucosal tissue.
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.
authors: Institute of Infection and Immunity, School of Medicine, Cardiff University, Heath Park, Cardiff, United Kingdom.
authors: Gabrielle
authors: G
authors: Stack
authors: Institute of Infection and Immunity, School of Medicine, Cardiff University, Heath Park, Cardiff, United Kingdom.
authors: Emma
authors: E
authors: Jones
authors: Institute of Infection and Immunity, School of Medicine, Cardiff University, Heath Park, Cardiff, United Kingdom.
authors: Morgan
authors: M
authors: Marsden
authors: Institute of Infection and Immunity, School of Medicine, Cardiff University, Heath Park, Cardiff, United Kingdom.
authors: Maria A
authors: MA
authors: Stacey
authors: Leukocyte Biology Section, National Heart and Lung Institute, Imperial College London, London, United Kingdom.
authors: Robert J
authors: RJ
authors: Snelgrove
authors: Division of Pathway Medicine and Edinburgh Infectious Diseases, University of Edinburgh, Edinburgh, United Kingdom.
authors: Paul
authors: P
authors: Lacaze
authors: Institute of Infection and Immunity, School of Medicine, Cardiff University, Heath Park, Cardiff, United Kingdom.
authors: Laura C
authors: LC
authors: Jacques
authors: Institute of Infection and Immunity, School of Medicine, Cardiff University, Heath Park, Cardiff, United Kingdom.
authors: Simone M
authors: SM
authors: Cuff
authors: Institute of Infection and Immunity, School of Medicine, Cardiff University, Heath Park, Cardiff, United Kingdom.
authors: Richard J
authors: RJ
authors: Stanton
authors: Institute of Infection and Immunity, School of Medicine, Cardiff University, Heath Park, Cardiff, United Kingdom.
authors: Awen M
authors: AM
authors: Gallimore
authors: Manchester Collaborative Centre for Inflammation Research (MCCIR), University of Manchester, Manchester, United Kingdom.
authors: Tracy
authors: T
authors: Hussell
authors: Institute of Infection and Immunity, School of Medicine, Cardiff University, Heath Park, Cardiff, United Kingdom.
authors: Gavin W G
authors: GW
authors: Wilkinson
authors: Division of Pathway Medicine and Edinburgh Infectious Diseases, University of Edinburgh, Edinburgh, United Kingdom.
authors: Peter
authors: P
authors: Ghazal
authors: Institute of Infection and Immunity, School of Medicine, Cardiff University, Heath Park, Cardiff, United Kingdom.
authors: Philip R
authors: PR
authors: Taylor
authors: Institute of Infection and Immunity, School of Medicine, Cardiff University, Heath Park, Cardiff, United Kingdom; Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, United Kingdom.
authors: Ian R
authors: IR
authors: Humphreys
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000276:immunology*; D003587:Cytomegalovirus / Q000276:immunology; D003586:Cytomegalovirus Infections / Q000276:immunology* / Q000378:metabolism; D004195:Disease Models, Animal; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D008562:Membrane Glycoproteins / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009092:Mucous Membrane / Q000276:immunology* / Q000821:virology*; D020411:Oligonucleotide Array Sequence Analysis
chemical_list: D015703:Antigens, CD; C492346:CD200 receptor, mouse; D008562:Membrane Glycoproteins; C042739:antigens, CD200
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