Platelets direct monocyte differentiation into epithelioid-like multinucleated giant foam cells with suppressive capacity upon mycobacterial stimulation.
Platelets direct monocyte differentiation into epithelioid-like multinucleated giant foam cells with suppressive capacity upon mycobacterial stimulation.
复制标题
血小板引导单核细胞分化为上皮样多核巨型泡沫细胞，对分枝杆菌刺激具有抑制能力。
DOI：
10.1093/infdis/jiu355
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发表时间：
2014-12-01
期刊：
影响因子：
--
通讯作者：
Kaufmann SH
中科院分区：
文献类型：
--
作者：
Feng Y;Dorhoi A;Mollenkopf HJ;Yin H;Dong Z;Mao L;Zhou J;Bi A;Weber S;Maertzdorf J;Chen G;Chen Y;Kaufmann SH
上皮样、泡沫状和多核巨细胞（MNGC）是结核肉芽肿的特征，但这些转化巨噬细胞的确切发生和功能尚不清楚。我们评估了血小板作为巨噬细胞转化驱动因子在分枝杆菌感染中的作用。方法：我们采用流式细胞术和显微镜来评估细胞表型和吞噬作用。 免疫分析允许量化的细胞因子和趋化因子，而基因微阵列技术被应用于估计全球转录组的变化。结核肉芽肿的免疫组化研究证实了我们在感染部位的发现。结果：在血小板存在下分化的单核细胞（MP-Macs）获得泡沫状上皮样外观并产生MNGC（MP-MNGC）。 MP-Macs上调活化标志物，吞噬分枝杆菌，并释放丰富的白细胞介素10。在延长培养后，MP-Macs与上皮样细胞和M2巨噬细胞共享转录特征，并上调CXCL 5转录物。与此一致，活动性结核病患者气道中的CXCL 5浓度显著增加。血小板特异性CD 42 b抗原在MP-Macs中检测到，同样在结核肉芽肿内的巨噬细胞、MNGC和上皮样细胞中检测到，沿着血小板聚集诱导因子PDPN。结论：血小板驱动巨噬细胞分化为MNGC，在结核肉芽肿中观察到上皮样、泡沫和巨细胞的特征。 我们的数据将血小板定义为结核病发病机制的新参与者。
Background. Epithelioid, foam, and multinucleated giant cells (MNGCs) are characteristics of tuberculosis granulomas, yet the precise genesis and functions of these transformed macrophages are unclear. We evaluated the role of platelets as drivers of macrophage transformation in mycobacterial infection. Methods. We employed flow cytometry and microscopy to assess cellular phenotype and phagocytosis. Immune assays allowed quantification of cytokines and chemokines, whereas gene microarray technology was applied to estimate global transcriptome alterations. Immunohistochemical investigations of tuberculosis granulomas substantiated our findings at the site of infection. Results. Monocytes differentiated in presence of platelets (MP-Macs) acquired a foamy, epithelioid appearance and gave rise to MNGCs (MP-MNGCs). MP-Macs up-regulated activation markers, phagocytosed mycobacteria, and released abundant interleukin 10. Upon extended culture, MP-Macs shared transcriptional features with epithelioid cells and M2 macrophages and up-regulated CXCL5 transcripts. In line with this, CXCL5 concentrations were significantly increased in airways of active tuberculosis patients. The platelet-specific CD42b antigen was detected in MP-Macs, likewise in macrophages, MNGCs, and epithelioid cells within tuberculosis granulomas, along with the platelet aggregation-inducing factor PDPN. Conclusions. Platelets drive macrophage differentiation into MNGCs with characteristics of epithelioid, foam, and giant cells observed in tuberculosis granulomas. Our data define platelets as novel participants in tuberculosis pathogenesis.
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