Della Chiesa Mariella, Romagnani Chiara, Thiel Andreas, Moretta Lorenzo, Moretta Alessandro
Dipartimento di Medicina Sperimentale, Sezione di Istologia, Via G.B. Marsano 10, 16132 Genova, Italy.
Blood. 2006 Dec 1;108(12):3851-8. doi: 10.1182/blood-2006-02-004028. Epub 2006 Jul 27.
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-alpha, in a CpG-dependent manner, whereas they induce IL-6 production in a CpG-independent manner. In turn pDC-derived IFN-alpha 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-alpha 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.
在天然免疫反应过程中，自然杀伤（NK）细胞可能与浆细胞样树突状细胞（pDC）和单核细胞衍生的树突状细胞（MDDC）相互作用。我们发现，新鲜分离的NK细胞以依赖CpG的方式促进pDC释放IFN-α，而它们以不依赖CpG的方式诱导IL-6产生。反过来，pDC衍生的IFN-α上调NK介导的杀伤作用，而IL-6可促进B细胞分化。我们还表明，暴露于外源性IL-12或与成熟的MDDC共培养会上调pDC依赖NK细胞的IFN-α产生。另一方面，与pDC共培养的NK细胞获得了杀伤未成熟MDDC的能力，从而有利于它们的编辑过程。最后，我们表明活化的NK细胞无法裂解pDC，因为这些细胞表现出对裂解的内在抗性。pDC暴露于IL-3会增加它们对NK细胞细胞毒性的敏感性，这是由于激活NK细胞受体的配体（如DNAM-1配体nectin-2）的从头表达所致。因此，不同的细胞间相互作用和各种细胞因子似乎控制着NK细胞、MDDC和pDC之间的多向网络，这可能在对病毒感染和肿瘤的天然免疫反应早期阶段发挥重要作用。
