以吞噬了结核菌的巨噬细胞以及各种变形巨噬细胞包括泡沫样细胞、泡沫样多核巨细胞、上皮样细胞为中心的结核肉芽肿的形成是结核病理发生的特征性标志；这些细胞一方面限制了结核菌的繁殖，另一方面又为结核菌潜伏和逃避免疫攻击提供了场所,但其分化来源尚不清楚。我们前期研究发现，血小板与人外周血单核细胞共培养，可诱导泡沫样多核巨细胞的产生增加，与结核菌细胞壁脂阿拉伯甘露糖（LAM）有协同作用；这些血小板诱导的变形巨噬细胞高表达上皮样细胞来源的CXCL5，以及免疫抑制性 M2细胞的特征性标志；与此相应，活动性结核病人肺泡灌洗液CXCL5水平明显增加，结核肉芽肿的变形细胞也表达血小板特异性抗原CD42b及与血小板聚集相关的抗原PDPN，提示血小板可能参与结核病理发生。本项目进一步从细胞、动物模型和临床标本研究血小板调节变形巨噬细胞产生的机制及在结核病理发生中的作用，研究结果将有助于对结核病发病机制的深入了解。

Epitheliod, foam and multinucleated giant cells (MNGCs) are characteristics of tuberculosis (TB) granulomas, yet the precise genesis and functions of these transformed macrophages are unclear. In our previous research, we found that monocytes differentiated in presence of platelets (MP-Macs) gave rise to more MNGCs. Early MP-Macs are activated and readily phagocytosed mycobacteria with abundant IL-10 releasing, while fully differentiated MP-Macs shared transcriptional features with epitheliod cells and M2 macrophages with upregulated CXCL5 transcripts. In line with this, CXCL5 concentrations were significantly increased in airways of active TB patients. The platelet-specific CD42b antigen and the platelet aggregation-inducing factor PDPN were abundantly expressed by macrophages, MNGCs and epitheliod cells within granulomas. Our data indicated platelet may play a role in TB pathogenesis. In this project, we aim at deciphering the roles of platelets (PLT) as drivers of transformed macrophage differentiation during TB pathogenesis. We will characterize PLT in specimens from TB patients and use a mouse TB model to identify the effects of PLT depletion on disease outcome and pathology.Transcriptomics and proteomics studies will enable us to build PLT signalosome and select TB-specific PLT-molecular signatures. PLT-molecular targets in TB will be validated by in vitro RNAi experiments and analysis in mouse mutants. Our results will add new information about PLT functions in TB pathogenesis, and may provide information relevant for other granulomatos diseases.??? ?