Division of Cell and Molecular Biology, Imperial College London, London, United Kingdom.
Blood. 2012 Nov 1;120(18):3729-40. doi: 10.1182/blood-2012-05-429977. Epub 2012 Sep 10.
Natural killer (NK) cells secrete lytic granules to directly kill virus-infected or transformed cells and secrete cytokines to communicate with other cells. Three-dimensional super-resolved images of F-actin, lytic granules, and IFN-γ in primary human NK cells stimulated through different activating receptors reveal that both IFN-γ and lytic granules accumulated in domains where the periodicity of the cortical actin mesh at the synapse opened up to be penetrable. Ligation of some activating receptors alone (eg, CD16 or NKG2D) was sufficient to increase the periodicity of the actin mesh, but surprisingly, ligation of others (eg, NKp46 or CD2) was not sufficient to induce cortical actin remodeling unless LFA-1 was coligated. Importantly, influenza virus particles that can be recognized by NK cells similarly did not open the actin mesh but could if LFA-1 was coligated. This leads us to propose that immune cells using germline-encoded receptors to directly recognize foreign proteins can use integrin recognition to differentiate between free pathogens and pathogen-infected cells that will both be present in blood. This distinction would not be required for NK cell receptors, such as NKG2D, which recognize host cell-encoded proteins that can only be found on diseased cells and not pathogens.
自然杀伤 (NK) 细胞分泌裂解颗粒以直接杀死病毒感染或转化的细胞，并分泌细胞因子与其他细胞进行通讯。通过不同的激活受体刺激的原代人 NK 细胞中 F-肌动蛋白、裂解颗粒和 IFN-γ的三维超分辨率图像显示，IFN-γ和裂解颗粒都在突触处皮质肌动蛋白网格周期性打开可穿透的区域积累。单独连接一些激活受体（例如 CD16 或 NKG2D）足以增加肌动蛋白网格的周期性，但令人惊讶的是，连接其他受体（例如 NKp46 或 CD2）不足以诱导皮质肌动蛋白重塑，除非共连接 LFA-1。重要的是，可被 NK 细胞识别的流感病毒颗粒同样不会打开肌动蛋白网格，但如果共连接 LFA-1 则可以。这使我们提出这样的假设，即使用种系编码受体直接识别外来蛋白的免疫细胞可以利用整合素识别来区分游离病原体和存在于血液中的感染细胞。对于 NK 细胞受体（例如 NKG2D），这种区分不是必需的，因为它们识别仅存在于患病细胞上而不存在于病原体上的宿主细胞编码蛋白。
