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Blood, 1 December 2006, Vol. 108, No. 12, pp. 3851-3858.
Prepublished online as a Blood First Edition Paper on July 27, 2006; DOI 10.1182/blood-2006-02-004028.
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IMMUNOBIOLOGY
Multidirectional interactions are bridging human NK cells with plasmacytoid and monocyte-derived dendritic cells during innate immune responses
Mariella Della Chiesa,
Chiara Romagnani,
Andreas Thiel,
Lorenzo Moretta, and
Alessandro Moretta
From the Dipartimento di Medicina Sperimentale (DIMES), Università di Genova, Genoa, Italy; German Rheumatism Research Centre, Clinical Immunology, Berlin, Germany; Istituto Giannina Gaslini Genova-Quarto, Genoa, Italy; and Centro di Eccellenza per la Ricerca Biomedica Genova, Genoa, Italy.
During innate immune responses, natural killer (NK) cells may interact with both plasmacytoid dendritic cells (pDCs) and monocyte-derived dendritic cells (MDDCs). We show that freshly isolated NK cells promote the release by pDCs of IFN- , in a CpG-dependent manner, whereas they induce IL-6 production in a CpG-independent manner. In turn pDC-derived IFN- up-regulates NK-mediated killing, whereas IL-6 could promote B-cell differentiation. We also show that exposure to exogenous IL-12 or coculture with maturing MDDCs up-regulates the NK-cell–dependent IFN- production by pDCs. On the other hand, NK cells cocultured with pDCs acquire the ability to kill immature MDDCs, thus favoring their editing process. Finally, we show that activated NK cells are unable to lyse pDCs because these cells display an intrinsic resistance to lysis. The exposure of pDCs to IL-3 increased their susceptibility to NK-cell cytotoxicity resulting from a de novo expression of ligands for activating NK-cell receptors, such as the DNAM-1 ligand nectin-2. Thus, different cell-to-cell interactions and various cytokines appear to control a multidirectional network between NK cells, MDDCs, and pDCs that is likely to play an important role during the early phase of innate immune responses to viral infections and to tumors.
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