Crosstalk between Dendritic Cells and Natural Killer Cells

Natural killer (NK) cells and dendritic cells (DCs) represent two distinct components of the innate immune system. NK cells act by their cytotoxic effects and cytokine production. DCs on the other hand recognize and present antigen, thus activating cells of the adaptive immune system. Emerging evidence suggests that there is interaction between NK cells and DCs at sites of inflammation and in lymph nodes. The crosstalk between NK cells and DCs is required for optimal immune cell expansion and activation.The interaction between NK cells and DCs during infection results in the production of cytokines from both cell types. For example, the IL-12 mediated DC activation of NK cells can lead to the production of TNF, GM-CSF and IFNγ. In turn, NK cells can activate DCs to produce cytokines such as IL-12, IL-6, TNF and type 1 IFN. These cytokines are responsible for the development of proinflammatory and adaptive immune responses. In addition to soluble mediators such as cytokines, DCs and NK cells activate one another reciprocally by cell-cell contact. This involves formation of immunological synapses by polarizing proteins such as Talin, Fascin, LFA-1, ICAM-3 and its ligand DC-SIGN. Reciprocal activation of the two cell types also occurs via the TNF family of proteins resulting in the production of IFNγ from NK cells and IL-12 from DCs.NK cells can upregulate the expression of co-stimulatory molecules on DCs such as CD80, CD86 and CD83 thus inducing maturation of DCs. In addition, NK cells are involved in the lysis of immature DCs via the NKp30 receptor as well as the CD94 receptor. Immature DCs express low levels of human leukocyte antigen-E (HLA-E), the ligand for CD94, and are thus susceptible to lysis by NK cells. The elimination of some immature DCs by NK cells represents a means of optimizing immune cell expansion leading to refinement of the immune response. Mature DC, on the other hand, can activate perforin and Fas-mediated cytotoxicity by NK cells.The interaction of NK cells and DC thus leads to reciprocal activation, DC maturation and immunoregulatory crosstalk. This pathway highlights the important molecular events involved in this crosstalk. (Upgraded 09/2019)