Super-resolution imaging of remodeled synaptic actin reveals different synergies between NK cell receptors and integrins
Super-resolution imaging of remodeled synaptic actin reveals different synergies between NK cell receptors and integrins
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DOI：
10.1182/blood-2012-05-429977
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发表时间：
2012-11-01
期刊：
影响因子：
20.3
通讯作者：
Davis, Daniel M.
中科院分区：
文献类型：
--
作者：
Brown, Alice C. N.;Dobbie, Ian M.;Davis, Daniel M.
自然杀伤（NK）细胞分泌溶解颗粒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沟通。通过不同活化受体刺激的原代人NK细胞中的F-肌动蛋白、溶解颗粒和IFN-γ的三维超分辨图像显示，IFN-γ和溶解颗粒都积累在突触处皮质肌动蛋白网格的周期性打开以可穿透的域中。一些激活受体单独的连接（如，CD 16或NKG 2D）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（如，NKp 46或CD 2）不足以诱导皮质肌动蛋白重塑，除非LFA-1被coligated。重要的是，可以被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LFA-1被coligated，则可以打开。这使我们提出，使用种系编码受体直接识别外源蛋白的免疫细胞可以使用整合素识别来区分血液中存在的游离病原体和病原体感染的细胞。NK细胞受体（如NKG 2D）不需要这种区别，它们识别宿主细胞编码的蛋白质，这些蛋白质只能在病变细胞上找到，而不能在病原体上找到。（血。2012; 120（18）：3729-3740）
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-gamma in primary human NK cells stimulated through different activating receptors reveal that both IFN-gamma 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. (Blood. 2012; 120(18):3729-3740)