Platelets Restrict the Oxidative Burst in Phagocytes and Facilitate Primary Progressive Tuberculosis
Platelets Restrict the Oxidative Burst in Phagocytes and Facilitate Primary Progressive Tuberculosis
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血小板限制吞噬细胞的氧化爆发并促进原发性进行性结核病
DOI：
10.1164/rccm.201910-2063oc
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发表时间：
2020-09-01
影响因子：
24.7
通讯作者：
Dorhoi, Anca
中科院分区：
文献类型：
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作者：
Scheuermann, Lisa;Pei, Gang;Dorhoi, Anca
理由：血小板在肺毛细血管中生成，控制止血，并发挥免疫功能。肺结核主要影响肺部，患者表现为血小板改变和咯血。血小板在肺结核免疫病理中的作用需要仔细评估。目的：确定呼吸组织中血小板的动态和相互作用伙伴，并确定其对肺结核预后的影响。方法：在小鼠原发性进行性肺结核模型中，通过血小板消耗和抗血小板药物的递送，分析对结核分枝杆菌感染变敏感的小鼠菌株。测量和主要结果：在实验性结核期间，血小板存在于感染部位，并与不同的髓细胞亚群形成聚集体。在肺结核患者中也检测到这种聚集物。血小板在感染的早期阶段是有害的，这种影响与它们的典型激活不耦合。血小板使肺细胞动力学和抗真菌t细胞反应模式保持不变，但通过限制肺内骨髓细胞活性氧的产生而阻碍了抗菌防御。结论：血小板在原发性进行性肺结核中是有害的，通过调节先天免疫反应来协调肺部免疫，并且可能适用于这种致命疾病的新干预措施。
Rationale: Platelets are generated in the capillaries of the lung, control hemostasis, and display immunological functions. Tuberculosis primarily affects the lung, and patients show platelet changes and hemoptysis. A role of platelets in immunopathology of pulmonary tuberculosis requires careful assessment.Objectives: To identify the dynamics and interaction partners of platelets in the respiratory tissue and establish their impact on the outcome of pulmonary tuberculosis.Methods: Investigations were primarily performed in murine models of primary progressive pulmonary tuberculosis, by analysis of mouse strains with variable susceptibility to Mycobacterium tuberculosis infection using platelet depletion and delivery of antiplatelet drugs.Measurements and Main Results: Platelets were present at the site of infection and formed aggregates with different myeloid subsets during experimental tuberculosis. Such aggregates were also detected in patients with tuberculosis. Platelets were detrimental during the early phase of infection, and this effect was uncoupled from their canonical activation. Platelets left lung cell dynamics and patterns of antimycobacterial T-cell responses unchanged but hampered antimicrobial defense by restricting production of reactive oxygen species in lung-residing myeloid cells.Conclusions: Platelets are detrimental in primary progressive pulmonary tuberculosis, orchestrate lung immunity by modulating innate immune responsiveness, and may be amenable to new interventions for this deadly disease.