The interaction of human natural killer cells with either unpolarized or polarized macrophages results in different functional outcomes
The interaction of human natural killer cells with either unpolarized or polarized macrophages results in different functional outcomes
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DOI：
10.1073/pnas.1007654108
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发表时间：
2010-12-14
影响因子：
11.1
通讯作者：
Bottino, Cristina
中科院分区：
文献类型：
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作者：
Bellora, Francesca;Castriconi, Roberta;Bottino, Cristina
先天免疫细胞之间的串扰可以极大地影响先天反应和适应性反应。在这里，我们分析了人类自然杀伤（NK）细胞和自体巨噬细胞之间的分子相互作用。活化的 NK 细胞杀死 M0 和 M2，而 M1 巨噬细胞由于 HLA I 类分子的表达较高，因此更能抵抗裂解。暴露于 LPS 或卡介苗后，M0 和 M2，而非极化（耐内毒素）M1 巨噬细胞，诱导静息 NK 细胞强烈活化。 CD69 和 CD25 激活标记物的表达以及针对肿瘤细胞和未成熟树突状细胞的细胞毒性的获得需要主要不依赖于接触的可溶性因子。相反，IFN-γ的产生是接触依赖性的，需要 DNAM-1 和 2B4（NK 上）与其巨噬细胞上的配体以及 IL-18 相互作用。 IL-18 还参与 NK 细胞获取 CCR7。有趣的是，M0 和 M2 细胞表达膜结合形式的 IL-18，在 LPS 处理后少量释放。我们的数据表明，在与暴露于微生物产品的 M0 巨噬细胞相互作用时，NK 细胞可能会放大经典的 1 型免疫反应。此外，M1 极化刺激可以将 M2 巨噬细胞从免疫调节状态中拯救出来，并塑造其功能行为以实现 NK 刺激能力。
The cross-talk among cells of the innate immunity can greatly affect both innate and adaptive responses. Here we analyzed the molecular interactions between human natural killer (NK) cells and autologous macrophages. Activated NK cells killed M0 and M2, whereas M1 macrophages were more resistant to lysis because of their higher expression of HLA class I molecules. Following exposure to LPS or bacillus Calmette-Guerin, M0 and M2, but not polarized (endotoxin tolerant) M1 macrophages, induced strong activation of resting NK cells. The expression of CD69 and CD25 activation markers and the acquisition of cytotoxicity against tumor cells and immature dendritic cells required soluble factors being mostly contact independent. On the contrary, IFN-gamma production was contact dependent and required the interaction of DNAM-1 and 2B4 (on NK) with their ligands on macrophages as well as IL-18. IL-18 was involved also in the acquisition of CCR7 by NK cells. Interestingly, M0 and M2 cells expressed a membrane-bound form of IL-18, which was released in small amounts after LPS treatment. Our data indicate that, upon interaction with M0 macrophages exposed to microbial products, NK cells may amplify classical type 1 immune responses. In addition, M1-polarizing stimuli can rescue M2 macrophages from their immunomodulatory state and shape their functional behavior toward NK stimulatory capability.