Ly49H+ NK cells migrate to and protect splenic white pulp stroma from murine cytomegalovirus infection.
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.
Bekiaris
Vasileios
V
Medical Research Council Centre for Immune Regulation, Birmingham Medical School, Birmingham, UK.
Timoshenko
Olga
O
Hou
Tie Zheng
TZ
Toellner
Kai
K
Shakib
Saba
S
Gaspal
Fabrina
F
McConnell
Fiona M
FM
Parnell
Sonia M
SM
Withers
David
D
Buckley
Chris D
CD
Sweet
Clive
C
Yokoyama
Wayne M
WM
Anderson
Graham
G
Lane
Peter J L
PJ
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
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