Platelet Activation and Apoptosis Modulate Monocyte Inflammatory Responses in Dengue
Platelet Activation and Apoptosis Modulate Monocyte Inflammatory Responses in Dengue
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DOI：
10.4049/jimmunol.1400091
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发表时间：
2014-08-15
影响因子：
4.4
通讯作者：
Bozza, Patricia T.
中科院分区：
文献类型：
--
作者：
Hottz, Eugenio D.;Medeiros-de-Moraes, Isabel M.;Bozza, Patricia T.
登革热是世界上最流行的人类虫媒病毒病。登革热感染的临床表现范围很广，从自限性发热性疾病到伴有出血和休克的严重综合征。血小板减少和血管渗漏伴血浆中细胞因子谱改变是重症登革热的特征。虽然单核细胞已被认为是登革热中细胞因子的重要来源，但血小板-单核细胞相互作用对登革热中炎症反应的贡献尚未得到解决。研究了登革热患者的血小板-单核细胞聚集体形成。血小板诱导的单核细胞的细胞因子反应和潜在的机制也进行了研究，在体外。我们观察到登革热患者血液样本中血小板-单核细胞聚集体水平增加，尤其是血小板减少和血管通透性增加的患者。此外，来自健康志愿者的单核细胞暴露于来自登革热患者的血小板诱导细胞因子IL-1 β、IL-8、IL-10和MCP-1的分泌，而暴露于来自健康志愿者的血小板仅诱导MCP-1的分泌。除了通过P-选择素结合活化血小板对单核细胞细胞因子应答的良好调节外，我们发现单核细胞与凋亡血小板的相互作用通过血小板-单核细胞聚集体中的磷脂酰丝氨酸识别介导IL-10分泌。此外，IL-10的分泌需要血小板单核细胞接触，而不是吞噬。总之，我们的研究结果表明，活化和凋亡血小板聚集与单核细胞在登革热感染和信号特异性细胞因子反应，可能有助于登革热的发病机制。
Dengue is the most prevalent human arbovirus disease in the world. Dengue infection has a large spectrum of clinical manifestations, from self-limited febrile illness to severe syndromes accompanied by bleeding and shock. Thrombocytopenia and vascular leak with altered cytokine profiles in plasma are features of severe dengue. Although monocytes have been recognized as important sources of cytokines in dengue, the contributions of platelet-monocyte interactions to inflammatory responses in dengue have not been addressed. Patients with dengue were investigated for platelet-monocyte aggregate formation. Platelet-induced cytokine responses by monocytes and underlying mechanisms were also investigated in vitro. We observed increased levels of platelet-monocyte aggregates in blood samples from patients with dengue, especially patients with thrombocytopenia and increased vascular permeability. Moreover, the exposure of monocytes from healthy volunteers to platelets from patients with dengue induced the secretion of the cytokines IL-1 beta, IL-8, IL-10 and MCP-1, whereas exposure to platelets from healthy volunteers only induced the secretion of MCP-1. In addition to the well-established modulation of monocyte cytokine responses by activated platelets through P-selectin binding, we found that interaction of monocytes with apoptotic platelets mediate IL-10 secretion through phosphatidylserine recognition in platelet-monocyte aggregates. Moreover, IL-10 secretion required plateletmonocyte contact but not phagocytosis. Together, our results demonstrate that activated and apoptotic platelets aggregate with monocytes during dengue infection and signal specific cytokine responses that may contribute to the pathogenesis of dengue.