Ly49H+ NK cells migrate to and protect splenic white pulp stroma from murine cytomegalovirus infection.
Bekiaris V., Timoshenko O., Hou TZ., Toellner K., Shakib S., Gaspal F., McConnell FM., Parnell SM., Withers D., Buckley CD., Sweet C., Yokoyama WM., Anderson G., Lane PJL.
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.