CD200 Receptor Restriction of Myeloid Cell Responses Antagonizes Antiviral Immunity and Facilitates Cytomegalovirus Persistence within Mucosal Tissue
Identifieur interne : 000715 ( Pmc/Curation ); précédent : 000714; suivant : 000716CD200 Receptor Restriction of Myeloid Cell Responses Antagonizes Antiviral Immunity and Facilitates Cytomegalovirus Persistence within Mucosal Tissue
Auteurs : Gabrielle Stack [Royaume-Uni] ; Emma Jones [Royaume-Uni] ; Morgan Marsden [Royaume-Uni] ; Maria A. Stacey [Royaume-Uni] ; Robert J. Snelgrove [Royaume-Uni] ; Paul Lacaze [Royaume-Uni] ; Laura C. Jacques [Royaume-Uni] ; Simone M. Cuff [Royaume-Uni] ; Richard J. Stanton [Royaume-Uni] ; Awen M. Gallimore [Royaume-Uni] ; Tracy Hussell [Royaume-Uni] ; Gavin W. G. Wilkinson [Royaume-Uni] ; Peter Ghazal [Royaume-Uni] ; Philip R. Taylor [Royaume-Uni] ; Ian R. Humphreys [Royaume-Uni]Source :
- PLoS Pathogens [ 1553-7366 ] ; 2015.
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
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DOI: 10.1371/journal.ppat.1004641
PubMed: 25654642
PubMed Central: 4412112
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Stacey</name><affiliation wicri:level="1"><nlm:aff id="aff001"><addr-line>Institute of Infection and Immunity, School of Medicine, Cardiff University, Heath Park, Cardiff, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Institute of Infection and Immunity, School of Medicine, Cardiff University, Heath Park, Cardiff</wicri:regionArea></affiliation></author><author><name sortKey="Snelgrove, Robert J" sort="Snelgrove, Robert J" uniqKey="Snelgrove R" first="Robert J." last="Snelgrove">Robert J. Snelgrove</name><affiliation wicri:level="1"><nlm:aff id="aff002"><addr-line>Leukocyte Biology Section, National Heart and Lung Institute, Imperial College London, London, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Leukocyte Biology Section, National Heart and Lung Institute, Imperial College London, London</wicri:regionArea></affiliation></author><author><name sortKey="Lacaze, Paul" sort="Lacaze, Paul" uniqKey="Lacaze P" first="Paul" last="Lacaze">Paul Lacaze</name><affiliation wicri:level="1"><nlm:aff id="aff003"><addr-line>Division of Pathway Medicine and Edinburgh Infectious Diseases, University of Edinburgh, Edinburgh, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Division of Pathway Medicine and Edinburgh Infectious Diseases, University of Edinburgh, Edinburgh</wicri:regionArea></affiliation></author><author><name sortKey="Jacques, Laura C" sort="Jacques, Laura C" uniqKey="Jacques L" first="Laura C." last="Jacques">Laura C. 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Cuff</name><affiliation wicri:level="1"><nlm:aff id="aff001"><addr-line>Institute of Infection and Immunity, School of Medicine, Cardiff University, Heath Park, Cardiff, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Institute of Infection and Immunity, School of Medicine, Cardiff University, Heath Park, Cardiff</wicri:regionArea></affiliation></author><author><name sortKey="Stanton, Richard J" sort="Stanton, Richard J" uniqKey="Stanton R" first="Richard J." last="Stanton">Richard J. Stanton</name><affiliation wicri:level="1"><nlm:aff id="aff001"><addr-line>Institute of Infection and Immunity, School of Medicine, Cardiff University, Heath Park, Cardiff, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Institute of Infection and Immunity, School of Medicine, Cardiff University, Heath Park, Cardiff</wicri:regionArea></affiliation></author><author><name sortKey="Gallimore, Awen M" sort="Gallimore, Awen M" uniqKey="Gallimore A" first="Awen M." last="Gallimore">Awen M. Gallimore</name><affiliation wicri:level="1"><nlm:aff id="aff001"><addr-line>Institute of Infection and Immunity, School of Medicine, Cardiff University, Heath Park, Cardiff, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Institute of Infection and Immunity, School of Medicine, Cardiff University, Heath Park, Cardiff</wicri:regionArea></affiliation></author><author><name sortKey="Hussell, Tracy" sort="Hussell, Tracy" uniqKey="Hussell T" first="Tracy" last="Hussell">Tracy Hussell</name><affiliation wicri:level="1"><nlm:aff id="aff004"><addr-line>Manchester Collaborative Centre for Inflammation Research (MCCIR), University of Manchester, Manchester, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Manchester Collaborative Centre for Inflammation Research (MCCIR), University of Manchester, Manchester</wicri:regionArea></affiliation></author><author><name sortKey="Wilkinson, Gavin W G" sort="Wilkinson, Gavin W G" uniqKey="Wilkinson G" first="Gavin W. G." last="Wilkinson">Gavin W. G. Wilkinson</name><affiliation wicri:level="1"><nlm:aff id="aff001"><addr-line>Institute of Infection and Immunity, School of Medicine, Cardiff University, Heath Park, Cardiff, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Institute of Infection and Immunity, School of Medicine, Cardiff University, Heath Park, Cardiff</wicri:regionArea></affiliation></author><author><name sortKey="Ghazal, Peter" sort="Ghazal, Peter" uniqKey="Ghazal P" first="Peter" last="Ghazal">Peter Ghazal</name><affiliation wicri:level="1"><nlm:aff id="aff003"><addr-line>Division of Pathway Medicine and Edinburgh Infectious Diseases, University of Edinburgh, Edinburgh, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Division of Pathway Medicine and Edinburgh Infectious Diseases, University of Edinburgh, Edinburgh</wicri:regionArea></affiliation></author><author><name sortKey="Taylor, Philip R" sort="Taylor, Philip R" uniqKey="Taylor P" first="Philip R." last="Taylor">Philip R. Taylor</name><affiliation wicri:level="1"><nlm:aff id="aff001"><addr-line>Institute of Infection and Immunity, School of Medicine, Cardiff University, Heath Park, Cardiff, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Institute of Infection and Immunity, School of Medicine, Cardiff University, Heath Park, Cardiff</wicri:regionArea></affiliation></author><author><name sortKey="Humphreys, Ian R" sort="Humphreys, Ian R" uniqKey="Humphreys I" first="Ian R." last="Humphreys">Ian R. Humphreys</name><affiliation wicri:level="1"><nlm:aff id="aff001"><addr-line>Institute of Infection and Immunity, School of Medicine, Cardiff University, Heath Park, Cardiff, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Institute of Infection and Immunity, School of Medicine, Cardiff University, Heath Park, Cardiff</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff005"><addr-line>Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire</wicri:regionArea></affiliation></author></analytic><series><title level="j">PLoS Pathogens</title><idno type="ISSN">1553-7366</idno><idno type="eISSN">1553-7374</idno><imprint><date when="2015">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>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 <italic>in vivo</italic> 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<sup>-/-</sup>) 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<sup>-/-</sup> 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 <italic>in vivo</italic>. 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.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Wright, Gj" uniqKey="Wright G">GJ Wright</name></author><author><name sortKey="Cherwinski, H" uniqKey="Cherwinski H">H Cherwinski</name></author><author><name sortKey="Foster Cuevas, M" uniqKey="Foster Cuevas M">M Foster-Cuevas</name></author><author><name sortKey="Brooke, G" uniqKey="Brooke G">G Brooke</name></author><author><name sortKey="Puklavec, Mj" uniqKey="Puklavec M">MJ Puklavec</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Barclay A, N" uniqKey="Barclay A N">N Barclay a</name></author><author><name sortKey="Wright, Gj" uniqKey="Wright G">GJ Wright</name></author><author><name sortKey="Brooke, G" uniqKey="Brooke G">G 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Fodor</name></author><author><name sortKey="Gibas, Cj" uniqKey="Gibas C">CJ Gibas</name></author></analytic></biblStruct></listBibl></div1></back></TEI><pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">PLoS Pathog</journal-id><journal-id journal-id-type="iso-abbrev">PLoS Pathog</journal-id><journal-id journal-id-type="publisher-id">plos</journal-id><journal-id journal-id-type="pmc">plospath</journal-id><journal-title-group><journal-title>PLoS Pathogens</journal-title></journal-title-group><issn pub-type="ppub">1553-7366</issn><issn pub-type="epub">1553-7374</issn><publisher><publisher-name>Public Library of Science</publisher-name><publisher-loc>San Francisco, CA USA</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">25654642</article-id><article-id pub-id-type="pmc">4412112</article-id><article-id pub-id-type="publisher-id">PPATHOGENS-D-14-01433</article-id><article-id pub-id-type="doi">10.1371/journal.ppat.1004641</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group></article-categories><title-group><article-title>CD200 Receptor Restriction of Myeloid Cell Responses Antagonizes Antiviral Immunity and Facilitates Cytomegalovirus Persistence within Mucosal Tissue</article-title><alt-title alt-title-type="running-head">CD200R Restricts Myeloid Cell Orchestration of Anti-CMV Immunity</alt-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Stack</surname><given-names>Gabrielle</given-names></name><xref ref-type="aff" rid="aff001"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Jones</surname><given-names>Emma</given-names></name><xref ref-type="aff" rid="aff001"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Marsden</surname><given-names>Morgan</given-names></name><xref ref-type="aff" rid="aff001"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Stacey</surname><given-names>Maria A.</given-names></name><xref ref-type="aff" rid="aff001"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Snelgrove</surname><given-names>Robert J.</given-names></name><xref ref-type="aff" rid="aff002"><sup>2</sup></xref></contrib><contrib contrib-type="author"><name><surname>Lacaze</surname><given-names>Paul</given-names></name><xref ref-type="aff" rid="aff003"><sup>3</sup></xref></contrib><contrib contrib-type="author"><name><surname>Jacques</surname><given-names>Laura C.</given-names></name><xref ref-type="aff" rid="aff001"><sup>1</sup></xref><xref ref-type="author-notes" rid="currentaff001"><sup>¤</sup></xref></contrib><contrib contrib-type="author"><name><surname>Cuff</surname><given-names>Simone M.</given-names></name><xref ref-type="aff" rid="aff001"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Stanton</surname><given-names>Richard J.</given-names></name><xref ref-type="aff" rid="aff001"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Gallimore</surname><given-names>Awen M.</given-names></name><xref ref-type="aff" rid="aff001"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Hussell</surname><given-names>Tracy</given-names></name><xref ref-type="aff" rid="aff004"><sup>4</sup></xref></contrib><contrib contrib-type="author"><name><surname>Wilkinson</surname><given-names>Gavin W. G.</given-names></name><xref ref-type="aff" rid="aff001"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Ghazal</surname><given-names>Peter</given-names></name><xref ref-type="aff" rid="aff003"><sup>3</sup></xref></contrib><contrib contrib-type="author"><name><surname>Taylor</surname><given-names>Philip R.</given-names></name><xref ref-type="aff" rid="aff001"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Humphreys</surname><given-names>Ian R.</given-names></name><xref ref-type="aff" rid="aff001"><sup>1</sup></xref><xref ref-type="aff" rid="aff005"><sup>5</sup></xref><xref ref-type="corresp" rid="cor001">*</xref></contrib></contrib-group><aff id="aff001"><label>1</label><addr-line>Institute of Infection and Immunity, School of Medicine, Cardiff University, Heath Park, Cardiff, United Kingdom</addr-line></aff><aff id="aff002"><label>2</label><addr-line>Leukocyte Biology Section, National Heart and Lung Institute, Imperial College London, London, United Kingdom</addr-line></aff><aff id="aff003"><label>3</label><addr-line>Division of Pathway Medicine and Edinburgh Infectious Diseases, University of Edinburgh, Edinburgh, United Kingdom</addr-line></aff><aff id="aff004"><label>4</label><addr-line>Manchester Collaborative Centre for Inflammation Research (MCCIR), University of Manchester, Manchester, United Kingdom</addr-line></aff><aff id="aff005"><label>5</label><addr-line>Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, United Kingdom</addr-line></aff><contrib-group><contrib contrib-type="editor"><name><surname>Hill</surname><given-names>Ann B.</given-names></name><role>Editor</role><xref ref-type="aff" rid="edit1"></xref></contrib></contrib-group><aff id="edit1"><addr-line>Oregon Health Sciences University, UNITED STATES</addr-line></aff><author-notes><fn fn-type="COI-statement" id="coi001"><p>The authors have declared that no competing interests exist.</p></fn><fn fn-type="con" id="contrib001"><p>Conceived and designed the experiments: GS EJ GWGW PRT IRH. Performed the experiments: GS EJ MM MAS RJS PL LCJ SMC IRH. Analyzed the data: GS EJ AMG RJS GWGW PG PRT IRH. Contributed reagents/materials/analysis tools: TH PG. Wrote the paper: GS IRH.</p></fn><fn fn-type="current-aff" id="currentaff001"><label>¤</label><p>Current address: Institute of Infection and Global Health, University of Liverpool, Liverpool, United Kingdom</p></fn><corresp id="cor001">* E-mail: <email>humphreysir@cardiff.ac.uk</email></corresp></author-notes><pub-date pub-type="collection"><month>2</month><year>2015</year></pub-date><pub-date pub-type="epub"><day>5</day><month>2</month><year>2015</year></pub-date><volume>11</volume><issue>2</issue><elocation-id>e1004641</elocation-id><history><date date-type="received"><day>19</day><month>6</month><year>2014</year></date><date date-type="accepted"><day>22</day><month>12</month><year>2014</year></date></history><permissions><copyright-statement>© 2015 Stack et al</copyright-statement><copyright-year>2015</copyright-year><copyright-holder>Stack et al</copyright-holder><license xlink:href="http://creativecommons.org/licenses/by/4.0/"><license-p>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.</license-p></license></permissions><self-uri content-type="pdf" xlink:type="simple" xlink:href="ppat.1004641.pdf"></self-uri><abstract><p>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 <italic>in vivo</italic> 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<sup>-/-</sup>) 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<sup>-/-</sup> 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 <italic>in vivo</italic>. 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.</p></abstract><abstract abstract-type="summary"><title>Author Summary</title><p>Immune inhibitory receptors, including CD200 receptor (CD200R), can limit immune responses in the mucosa to restrict reactivity to the plethora of harmless antigens that mucosal surfaces are continually exposed to. However, viruses may exploit these suppressive mechanisms to enable their persistence and spread. Many viruses, including herpesviruses, have acquired functional homologs of CD200, the ligand of CD200R, implying that viral exploitation of this pathway is evolutionary advantageous. We now show that the β-herpesvirus murine cytomegalovirus (MCMV) takes advantage of the CD200R inhibitory pathway to persist within a mucosal site of MCMV persistence, the salivary glands. Mice deficient in CD200R mounted elevated antiviral immune responses that were driven by the increased division and accumulation of myeloid cells that function to orchestrate the generation of antiviral effector immune responses. Interestingly, MCMV infection of myeloid cells up-regulated CD200 expression. Thus, MCMV exploits the CD200 pathway to persist within mucosal tissue.</p></abstract><funding-group><funding-statement>This work was supported by a Wellcome Trust Senior Research Fellowship in Basic Biomedical Science (WT098026MA, to IRH), an MRC Senior Fellowship (G0601617/1 to PRT) and a President’s Scholarship (to GS). PG was supported by the Wellcome Trust (WT066784) and by the BBSRC/EPSRC (BB/D019621/1). PL was supported by a BBSRC studentship. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.</funding-statement></funding-group><counts><fig-count count="6"></fig-count><table-count count="0"></table-count><page-count count="0"></page-count></counts><custom-meta-group><custom-meta id="data-availability"><meta-name>Data Availability</meta-name><meta-value>All relevant data are within the paper and its Supporting Information files.</meta-value></custom-meta></custom-meta-group></article-meta><notes><title>Data Availability</title><p>All relevant data are within the paper and its Supporting Information files.</p></notes></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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