Natural killer cells as an initial defense against pathogens

Abstract

Natural killer (NK) cells serve as a crucial first line of defense against tumors and a diverse range of pathogens. Recognition of infection by NK cells is accomplished by the activation of receptors on the NK cell surface, which initiate NK cell effector functions. Many of the receptors and ligands involved in NK cell antimicrobial activity have been identified, and we are beginning to appreciate how they function during infection. In addition, NK cells are activated by cytokines (e.g. interleukin 12 and type I interferons), which are products of activated macrophages and dendritic cells. In response to these activating stimuli, NK cells secrete cytokines and chemokines and lyse target cells. Recent studies have focused on the mechanisms by which NK cells recognize and respond to viruses, parasites and bacteria, and on the unique role of NK cells in innate immunity to infection.

Figure 1

Interaction between DCs and NK cells during MCMV infection. (a) MCMV infection activates DCs to produce IFN-α, IFN-β and IL-12 by a MyD88- and TLR9-dependent pathway, as shown in (b). IFN-α, IFN-β and IL-12 are potent activators of NK cell IFN-γ secretion and cytotoxic activity, which are crucial for NK cell control of infection.