Natural killer and dendritic cell liaison: recent insights and open questions.

The functional links between natural killer (NK) and dendritic cells (DCs) have been widely investigated in the last years and different studies have demonstrated that reciprocal activations ensue upon NK/DC interactions. More recently, the anatomical sites were these interactions take place have been identified together with the related cell subsets involved. Remarkably, as predicted by pioneering studies, there is now "in vivo" evidence that this cellular cross-talk occurring during the innate phase of the immune response can deeply affects the magnitude and the quality of the subsequent adaptive response. Thus, NK cells are not merely cytotoxic lymphocytes competent in containing viral and tumor spreading but can now rather be considered as crucial fine-tuning effector cells. Despite the large mass of information rapidly obtained in this field, several fundamental questions still remain to be addressed. Among them, two central issues require additional consideration: (a) what mediates the activation of NK cell cytotoxicity induced by DCs and (b) what factors are responsible for NK-dependent maturation of DCs. Unexpectedly, for both of these questions insufficient or inconsistent results are so far available; factors either dependent or independent from cell contacts between DCs and NK cells have been convincingly described, and it is likely that several mechanisms, rather than a single one, are responsible for each of these novel innate functions. Understanding the molecular bases of this complex liaison will pave the way to new and more effective immune adjuvants. The most recent advances about NK/DC interplay are here reviewed and possible answers to still open questions in this field are considered.