Multi-directional cross-regulation of NK cell function during innate immune responses.

In recent years a number of studies allowed major advances in our understanding of different cell types of the innate immunity and of the role they play during the early phases of infections. Some of these cells, such as mast cells, endothelial cells and certain immature dendritic cells (iDCs), are resident within peripheral tissues, while others, including NK cells, are rapidly recruited from blood stream. These studies indicated that innate immunity cells interact each other in inflamed tissues and in secondary lymphoid organs leading to modulation or amplification of different innate effector mechanisms and that a large array of microbial products can directly activate different effector cells of the innate immunity, also including NK cells. The final outcome of these cellular interactions may have dramatic impact on the quality and strength of down-stream adaptive immune responses. Noticeably, the effect on the adaptive immunity can result not only from the action of polarizing cytokines such as IL12 or IL4, but also from the NK-mediated "DC editing" leading to the selection of the most suitable DCs for subsequent priming of Th1 cell responses. Thus classical innate effector cells can also be viewed as regulatory cells that play a pivotal role in defenses against pathogens.