DC-dependent activation of NK cells. NK cells are involved in early viral control and by interacting with DCs they have a crucial role of producing pro-inflammatory cytokines and lysing infected cells. In addition, they can interact with T cells and DCs to shape the magnitude and quality of adaptive immune responses. [66] [67] [68] Following tissue invasion by pathogens and subsequent initiation of inflammatory responses, NK cells migrate to lymphoid tissues in response to the chemokines IL-8 and fractalkine (CX3CL1). In a mouse model, Lucas et al. 69 showed that, in vivo, naive NK cells do not acquire effector function unless a priming step has occurred by contact with DCs in draining lymph nodes. The requirements for NK priming was independent of IL-12 and it included secretion of IFN-a by TLR þ cells, which induced upregulation of IL-15Ra and IL-15 expression by DCs, and trans-presentation of IL-15 by DCs to NK cells in the lymph node. NK cells are not fully activated during priming by DCs, as they do not spontaneously produce IFN-g or mediate cytotoxicity. Full activation of NK cells requires an additional contact with mDCs. This results in mutual activation of previously primed NK cells and DC, 70 and in the release of IFN-g by NK cells, thus contributing to antigen-driven T-cell activation. 71 Blocking of IL-12 abolishes DC-induced IFN-g secretion by NK cells, whereas membrane-bound IL-15 on DCs is essential for NK cell proliferation and survival 72 ( Figure 2 ).