Cross-Talks between Natural Killer Cells and Distinct Subsets of Dendritic Cells

Abstract

In recent years, the essential role of bi-directional cross-talk between natural killer (NK) and dendritic cells (DC) during immune responses has been clearly elucidated. In particular, this cross-talk results in the development of an efficient innate response, through DC-mediated NK cell activation, and a potent adaptive immune response, through NK-mediate DC editing and maturation. Recently, some novel human DC subsets have been identified: migratory DCs in afferent lymph and draining lymph nodes; CLEC9A(+)/BDCA3(+) (CD141) DCs in interstitial dermis, liver, lung; inflammatory DCs in several inflammatory fluids. At the same time, it has been shown that also human NK cells are present in these compartments. Here, we will review the most recent findings on NK/DC cross-talk and we will discuss the necessity of acquiring more complete knowledge about these interactions in view of the new information available on both DC and NK cell subsets.

Keywords: Th1 cells; cross-priming; dendritic cells; humans; natural killer cells.

Figure 1

DCs subsets may differently affect NK cell function. Distinct DC subsets reflect different capability to promote NK cell function: IL-15 released by LC may promote NK cell proliferation; IL-12, mainly produced by CLEC9A⁺/BDCA3⁺ DCs and BDCA1⁺ DCs, induces IFN-γ release and subsequent Th1 polarization of T cells; NK cytolytic activity may be boosted by IFN-α secreted by pDCs and CLEC9A⁺/BDCA3⁺ DCs.

Figure 2

NK/DC cross-talk. The interaction between NK cells and DCs results in reciprocal activation: mature DCs release cytokines able to promote NK cell activation (all myeloid mature DCs can produce IL-12 whereas pDCs and CLEC9A⁺ BDCA3⁺ DCs can release large amounts of IFN-α); in turn, IFN-γ released by activated NK cells promotes Th1 polarization and, together with TNF, DC maturation, and migration to draining lymph nodes. Activated NK cells can also lyse tumor cells, leading to the generation of tumor antigenic material; tumor debris are then engulfed by DCs and tumor antigens are processed and presented by mature DCs to both CD8⁺ (cross-priming) and CD4⁺ T cells.