title: Ly49H+ NK cells migrate to and protect splenic white pulp stroma from murine cytomegalovirus infection.
abstract: In this study, we show that in the absence of a protective NK cell response, murine CMV causes destruction of splenic white and red pulp pulp areas in the first few days of infection. Destruction of T zone stroma is associated with almost complete loss of dendritic cells and T cells. We provide evidence that the virus replicates in red and white pulp stroma in vivo and in vitro. Control of white pulp viral replication is associated with migration of murine CMV-specific activated NK cells to white pulp areas, where they associate directly with podoplanin-expressing T zone stromal cells. Our data explain how NK cells protect the lymphoid-rich white pulp areas from CMV, allowing protective adaptive T cell-dependent immune responses to develop, and how this mechanism might break down in immunocompromised patients.
authors.affiliation: Medical Research Council Centre for Immune Regulation, Birmingham Medical School, Birmingham, UK.
authors.forename: Vasileios
authors.initials: V
authors.lastname: Bekiaris
authors.forename: Olga
authors.initials: O
authors.lastname: Timoshenko
authors.forename: Tie Zheng
authors.initials: TZ
authors.lastname: Hou
authors.forename: Kai
authors.initials: K
authors.lastname: Toellner
authors.forename: Saba
authors.initials: S
authors.lastname: Shakib
authors.forename: Fabrina
authors.initials: F
authors.lastname: Gaspal
authors.forename: Fiona M
authors.initials: FM
authors.lastname: McConnell
authors.forename: Sonia M
authors.initials: SM
authors.lastname: Parnell
authors.forename: David
authors.initials: D
authors.lastname: Withers
authors.forename: Chris D
authors.initials: CD
authors.lastname: Buckley
authors.forename: Clive
authors.initials: C
authors.lastname: Sweet
authors.forename: Wayne M
authors.initials: WM
authors.lastname: Yokoyama
authors.forename: Graham
authors.initials: G
authors.lastname: Anderson
authors.forename: Peter J L
authors.initials: PJ
authors.lastname: Lane
mesh_terms: D000818:Animals; D000950:Antigens, Ly / Q000378:metabolism*; D054357:Chemokine CXCL10 / Q000378:metabolism; D054371:Chemokine CXCL11 / Q000378:metabolism; D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D005434:Flow Cytometry; D006566:Herpesviridae Infections / Q000276:immunology*; D007150:Immunohistochemistry; D007694:Killer Cells, Natural / Q000378:metabolism*; D007834:Lasers; D037181:Lectins, C-Type / Q000378:metabolism*; D051379:Mice; D042282:Microdissection; D018613:Microscopy, Confocal; D018146:Muromegalovirus / Q000276:immunology; D055650:NK Cell Lectin-Like Receptor Subfamily A; D054367:Receptors, CXCR3 / Q000378:metabolism; D055630:Receptors, NK Cell Lectin-Like; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000276:immunology / Q000473:pathology / Q000821:virology*; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000950:Antigens, Ly; D054357:Chemokine CXCL10; D054371:Chemokine CXCL11; C515188:Cxcr3 protein, mouse; C527096:Klra8 protein, mouse; D037181:Lectins, C-Type; D055650:NK Cell Lectin-Like Receptor Subfamily A; D054367:Receptors, CXCR3; D055630:Receptors, NK Cell Lectin-Like