Center for Experimental and Molecular Medicine, Amsterdam University Medical Center (UMC), University of Amsterdam, The Netherlands.
Department of Medicine, University of Cambridge, United Kingdom.
J Infect Dis. 2019 Jan 29;219(4):648-659. doi: 10.1093/infdis/jiy541.
Infection with the gram-negative bacillus Burkholderia pseudomallei (melioidosis) is an important cause of pneumosepsis in Southeast Asia and has a mortality of up to 40%. We aimed to assess the role of platelets in the host response against B. pseudomallei infection.
Association between platelet counts and mortality was determined in 1160 patients with culture-proven melioidosis. Mice treated with (low- or high-dose) platelet-depleting antibody were inoculated intranasally with B. pseudomallei and killed. Additional studies using functional glycoprotein Ibα-deficient mice were conducted.
Thrombocytopenia was present in 31% of patients at admission and predicted mortality in melioidosis patients even after adjustment for confounders. In our murine-melioidosis model, platelet counts decreased, and mice treated with a platelet-depleting antibody showed enhanced mortality and higher bacterial loads compared to mice with normal platelet counts. Low platelet counts had a modest impact on early-pulmonary neutrophil influx. Reminiscent of their role in hemostasis, platelet depletion impaired vascular integrity, resulting in early lung bleeding. Glycoprotein Ibα-deficient mice had reduced platelet counts during B. pseudomallei infection together with an impaired local host defense in the lung.
Thrombocytopenia predicts mortality in melioidosis patients and, during experimental melioidosis, platelets play a protective role in both innate immunity and vascular integrity.
革兰氏阴性杆菌伯克霍尔德菌（类鼻疽）感染是东南亚气性坏疽的重要病因，死亡率高达 40%。我们旨在评估血小板在宿主对抗伯克霍尔德菌感染反应中的作用。
我们在 1160 例经培养证实的类鼻疽患者中确定血小板计数与死亡率之间的关联。用（低剂量或高剂量）血小板耗竭抗体处理的小鼠经鼻腔接种伯克霍尔德菌，并将其杀死。还进行了使用功能性糖蛋白 Ibα缺陷型小鼠的额外研究。
入院时 31%的患者存在血小板减少症，即使在调整混杂因素后，血小板减少症仍可预测类鼻疽患者的死亡率。在我们的类鼻疽小鼠模型中，血小板计数下降，用血小板耗竭抗体治疗的小鼠与血小板计数正常的小鼠相比，死亡率更高，细菌负荷更高。低血小板计数对早期肺中性粒细胞浸润有一定影响。与止血中的作用相似，血小板耗竭会损害血管完整性，导致早期肺出血。在类鼻疽感染期间，糖蛋白 Ibα缺陷型小鼠的血小板计数减少，肺局部宿主防御能力受损。
血小板减少症可预测类鼻疽患者的死亡率，并且在实验性类鼻疽中，血小板在固有免疫和血管完整性中均发挥保护作用。
