Platelet Activation and the Immune Response to Tuberculosis.
Platelet Activation and the Immune Response to Tuberculosis.
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DOI：
10.3389/fimmu.2021.631696
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发表时间：
2021
影响因子：
7.3
通讯作者：
Friedland JS
中科院分区：
文献类型：
--
作者：
Kirwan DE;Chong DLW;Friedland JS
2019年，有1000万人出现症状性结核病，120万人死亡。在活动性TB中，炎症反应引起组织破坏，这导致急性发病率和死亡率。TB中的组织破坏由宿主先天免疫驱动并通过酶介导，主要是基质金属蛋白酶（MMP），其由白细胞和基质细胞分泌并降解细胞外基质。在这里，我们审查了越来越多的证据牵连血小板在结核病的免疫病理学。结核病患者通常具有与疾病严重程度相关的高血小板计数和高凝状态。人结核肉芽肿中存在血小板，结核病患者与健康对照组相比血小板相关基因转录物增加。血小板最有可能通过其对其他免疫细胞（特别是单核细胞）的作用来驱动TB免疫病理学，从而导致活化标志物的上调、MMP分泌增加和吞噬作用增强。最后，我们认为目前的证据支持在结核病治疗中使用靶向抗血小板药物，因为越来越多的人对开发宿主导向疗法以限制组织损伤和改善治疗结果感兴趣。总之，血小板与TB疾病有关，并通过其与其他白细胞的细胞相互作用促进MMP介导的组织损伤，并且是新型宿主导向疗法的潜在靶点。
In 2019 10 million people developed symptomatic tuberculosis (TB) disease and 1.2 million died. In active TB the inflammatory response causes tissue destruction, which leads to both acute morbidity and mortality. Tissue destruction in TB is driven by host innate immunity and mediated via enzymes, chiefly matrix metalloproteinases (MMPs) which are secreted by leukocytes and stromal cells and degrade the extracellular matrix. Here we review the growing evidence implicating platelets in TB immunopathology. TB patients typically have high platelet counts, which correlate with disease severity, and a hypercoagulable profile. Platelets are present in human TB granulomas and platelet-associated gene transcripts are increased in TB patients versus healthy controls. Platelets most likely drive TB immunopathology through their effect on other immune cells, particularly monocytes, to lead to upregulation of activation markers, increased MMP secretion, and enhanced phagocytosis. Finally, we consider current evidence supporting use of targeted anti-platelet agents in the treatment of TB due to growing interest in developing host-directed therapies to limit tissue damage and improve treatment outcomes. In summary, platelets are implicated in TB disease and contribute to MMP-mediated tissue damage via their cellular interactions with other leukocytes, and are potential targets for novel host-directed therapies.
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DOI：
10.1183/13993003.02325-2014
发表时间：
2015-10
期刊：
The European respiratory journal
影响因子：
--
作者：
Amaral AF;Coton S;Kato B;Tan WC;Studnicka M;Janson C;Gislason T;Mannino D;Bateman ED;Buist S;Burney PG;BOLD Collaborative Research Group
通讯作者：
BOLD Collaborative Research Group
DOI：
10.1038/s41579-018-0013-4
发表时间：
2018-08
期刊：
Nature reviews. Microbiology
影响因子：
--
作者：
Ehrt S;Schnappinger D;Rhee KY
通讯作者：
Rhee KY
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
20.3
作者：
Andonegui, G;Kerfoot, SM;Kubes, P
通讯作者：
Kubes, P
影响因子：
2.8
作者：
Denkin, S;Byrne, S;Zhang, Y
通讯作者：
Zhang, Y