NKT cells are essential for innate immune control of vaccinia viral infection in vivo (108.3)

Abstract The role of natural killer T (NKT) cells during the innate immune response to pathogen remains incompletely defined. We previously showed that early control of vaccinia virus is critically dependent on the activation of natural killer (NK) cells. Here we show that in CD1d-deficient hosts, early control of vaccinia virus is compromised. This defect in viral clearance corresponds to an insufficient NK cell response, as NK cells from CD1d-deficient hosts have reduced production of the effector molecules IFN-γ and Granzyme B. Furthermore, NK cells from infected CD1d-deficient mice fail to lyse target cells when used in a chromium release assay. These data suggest a role for NKT cells in NK cell activation. In vitro, NK cell activation in response to vaccinia is dependent on both dendritic cells (DC) and NKT cells. We observe that NKT cells produce high levels of IFN-γ in response to vaccinia virus, and the production of IL-12 by DC is dependent on NKT cell presence. Direct contact between NKT cells and DC is required to fully license them to effectively activate NK cells, a phenomenon that may be attributed to upregulation of activating NK ligands RAE-1 and MULT-1 on DC surfaces. Overall, our data show that NKT cells are required for the activation of NK cells during vaccinia infection and suggest that NKT cells license DC to optimally activate NK cells. These data indicate that NKT cells are key players in the early generation of an innate immune response to viral infection.