Ly49H+ NK cells migrate to and protect splenic white pulp stroma from murine cytomegalovirus infection |
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Authors: | Bekiaris Vasileios Timoshenko Olga Hou Tie Zheng Toellner Kai Shakib Saba Gaspal Fabrina McConnell Fiona M Parnell Sonia M Withers David Buckley Chris D Sweet Clive Yokoyama Wayne M Anderson Graham Lane Peter J L |
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Institution: | Medical Research Council Centre for Immune Regulation, Birmingham Medical School, Birmingham, UK. |
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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. |
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