Platelets accumulate in lung lesions of tuberculosis patients and inhibit T-cell responses and Mycobacterium tuberculosis replication in macrophages.
Platelets accumulate in lung lesions of tuberculosis patients and inhibit T-cell responses and Mycobacterium tuberculosis replication in macrophages.
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DOI：
10.1002/eji.202149549
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发表时间：
2022-05
影响因子：
5.4
通讯作者：
中科院分区：
文献类型：
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血小板调节导致疾病的人体炎症反应。然而，血小板在结核病发病机制中的作用尚不清楚。在这里，我们发现活动性结核病患者外周血中血小板数量多，淋巴细胞数量少，导致血小板与淋巴细胞比（PL比）高。此外，活动性结核患者血清中促进血小板分化或与血小板活化相关的不同介质浓度升高。免疫组化分析显示，肺肉芽肿病变周围有血小板，与T淋巴细胞和巨噬细胞密切接触。对人肺结核肉芽肿干酪样组织的转录组学分析和基因本体分析显示，与正常肺组织相比，53个血小板活化相关基因高表达。体外活化的血小板（或其上清液）抑制BCG诱导的T淋巴细胞增殖和IFN - γ的产生。同样，血小板抑制结核分枝杆菌细胞内巨噬细胞的生长。活化血小板释放的可溶性因子介导免疫和结核分枝杆菌复制活动。此外，蛋白质组学和中和研究（通过单克隆抗体）发现TGF - β和PF4分别是抑制T细胞反应和增强巨噬细胞杀分枝杆菌活性的因素。总之，这些结果突出了血小板在结核发病中的重要性。血小板在对抗结核分枝杆菌的免疫反应中起着重要作用。它们存在于感染部位；它们可以下调T淋巴细胞的增殖和细胞因子的产生，并可能增强巨噬细胞的效应功能，减少分枝杆菌的复制。
Platelets regulate human inflammatory responses that lead to disease. However, the role of platelets in tuberculosis (TB) pathogenesis is still unclear. Here, we show that patients with active TB have a high number of platelets in peripheral blood and a low number of lymphocytes leading to a high platelets to lymphocytes ratio (PL ratio). Moreover, the serum concentration of different mediators promoting platelet differentiation or associated with platelet activation is increased in active TB. Immunohistochemistry analysis shows that platelets localise around the lung granuloma lesions in close contact with T lymphocytes and macrophages. Transcriptomic analysis of caseous tissue of human pulmonary TB granulomas, followed by Gene Ontology analysis, shows that 53 platelet activation‐associated genes are highly expressed compared to the normal lung tissue. In vitro activated platelets (or their supernatants) inhibit BCG‐induced T‐ lymphocyte proliferation and IFN‐γ production. Likewise, platelets inhibit the growth of intracellular macrophages of Mycobacterium (M.) tuberculosis. Soluble factors released by activated platelets mediate both immunological and M. tuberculosis replication activities. Furthermore, proteomic and neutralisation studies (by mAbs) identify TGF‐β and PF4 as the factors responsible for inhibiting T‐cell response and enhancing the mycobactericidal activity of macrophages, respectively. Altogether these results highlight the importance of platelets in TB pathogenesis. Platelets are important players in the immune response against Mycobacterium tuberculosis. They are present at the site of infection; they can downregulate the proliferation and cytokine production of T lymphocytes, and they may enhance the effector function of macrophages, decreasing mycobacterial replication.
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影响因子：
3
作者：
Inui M;Tazawa K;Kishi Y;Takai T
通讯作者：
Takai T
影响因子：
7.3
作者：
Kirwan DE;Chong DLW;Friedland JS
通讯作者：
Friedland JS
影响因子：
8
作者：
Gollomp, Kandace;Kim, Minna;Poncz, Mortimer
通讯作者：
Poncz, Mortimer
DOI：
10.1093/bioinformatics/btn615
发表时间：
2009-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Carbon S;Ireland A;Mungall CJ;Shu S;Marshall B;Lewis S;AmiGO Hub;Web Presence Working Group
通讯作者：
Web Presence Working Group
影响因子：
11.1
作者：
Griesshammer, M;Bangerter, M;Heimpel, H
通讯作者：
Heimpel, H