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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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Submitted February 21, 2006
Accepted July 16, 2006
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*
Dipartimento di Medicina Sperimentale (DI.ME.S.), Universita di Genova, Genova, Italy
German Rheumatism Research Centre, Clinical Immunology, Berlin, Germany
Istituto Giannina Gaslini Genova-Quarto, Italy
* Corresponding author; email: alemoret{at}unige.it.
During innate immune responses natural killer cells (NK) may interact with both plasmacytoid dendritic cells (pDC) and monocyte-derived dendritic cells (MDDC). We show that freshly isolated NK cells promote the release by pDCs of IFN- , in a CpG-dependent manner, while they induce IL-6 production in a CpG-independent manner. In turn pDC-derived IFN- upregulates NK-mediated killing while IL-6 could promote B cell differentiation. We also show that exposure to exogenous IL-12 or co-culture with maturing MDDCs upregulates the NK cell-dependent IFN- production by pDCs. On the other hand NK cells co-cultured with pDCs acquire the ability to kill immature MDDCs, thus favouring their editing process. Finally we show that activated NK cells are unable to lyse pDCs since 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, 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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