Human NK cells directly recognize Mycobacterium bovis via TLR2 and acquire the ability to kill monocyte-derived DC
Human NK cells directly recognize Mycobacterium bovis via TLR2 and acquire the ability to kill monocyte-derived DC
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DOI：
10.1093/intimm/dxn073
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发表时间：
2008-09-01
影响因子：
4.4
通讯作者：
Moretta, Alessandro
中科院分区：
文献类型：
--
作者：
Marcenaro, Emanuela;Ferranti, Bruna;Moretta, Alessandro
NK细胞是早期先天防御各种病原体的重要参与者。在这项研究中，我们研究了人类NK细胞与牛分枝杆菌（bacille Calmette-Guerin， BCG）之间的相互作用，并确定了这种相互作用是否以及如何影响NK细胞的活化、细胞因子的产生和细胞毒性。我们发现，高度纯化的NK细胞在与BCG短期共培养后，表达了包括CD69和CD25在内的激活标记物。此外，这些NK细胞释放ifn - γ和肿瘤坏死因子- α，并更有效地杀死不同的靶标，包括单核细胞来源的未成熟树突状细胞。所有这些功能在外源IL-12的存在下都被强烈上调。虽然在显示NCRbright表型的NK细胞群中检测到更有效的应答，但没有直接证据表明触发NK受体参与卡介苗识别。另一方面，抗toll样受体（TLR）2 mAb抑制NK细胞对BCG的应答，提示NK细胞可能表达功能性TLR2，并在其直接识别BCG的机制中发挥作用。综上所述，这些数据表明，BCG通过NK细胞和抗原呈递细胞的“共享”TLR2诱导其同时激活，可以促进NK细胞和树突状细胞之间有效的双向相互作用，这是随后启动TO反应所必需的。
NK cells are important players of the early innate defense against various pathogens. In this study, we investigated the interaction between human NK cells and Mycobacterium bovis [bacille Calmette-Guerin (BCG)] and we determined whether and how such an interaction might impact on NK cell activation, cytokine production and cytotoxicity. We show that highly purified NK cells, upon short-term co-culture with BCG, expressed activation markers including CD69 and CD25. Moreover, these NK cells released IFN-gamma and tumor necrosis factor-alpha and killed more efficiently different targets including monocyte-derived immature dendritic cell. All these functions were strongly up-regulated in the presence of exogenous IL-12. Although more efficient responses were detected in NK cell populations displaying an NCRbright phenotype, no direct evidence of an involvement of triggering NK receptors in BCG recognition could be obtained. On the other hand, anti-toll-like receptor (TLR)2 mAb inhibited NK cell responses to BCG, suggesting that NK cells may express a functional TLR2, which plays a role in their mechanism of direct BCG recognition. Taken together, these data suggest that BCG, by inducing simultaneous activation of NK and antigen-presenting cells via their 'shared' TLR2, can promote efficient bidirectional NK-dendritic cell interactions necessary for subsequent priming of TO responses.