Peroxisome proliferator-activated receptor γ-retinoid X receptor agonists increase CD36-dependent phagocytosis of Plasmodium falciparum-parasitized erythrocytes and decrease malaria-induced TNF-α secretion by monocytes/macrophages
Peroxisome proliferator-activated receptor γ-retinoid X receptor agonists increase CD36-dependent phagocytosis of Plasmodium falciparum-parasitized erythrocytes and decrease malaria-induced TNF-α secretion by monocytes/macrophages
复制标题
DOI：
10.4049/jimmunol.166.11.6742
复制
发表时间：
2001-06-01
影响因子：
4.4
通讯作者：
Kain, KC
中科院分区：
文献类型：
--
作者：
Serghides, L;Kain, KC
严重和致命的疟疾与宿主防御系统未能控制寄生虫复制、过度分泌促炎细胞因子(如肿瘤坏死因子-α)以及重要器官中寄生的红细胞(PE)隔离有关。CD36是一种主要的隔离受体，这使得人们认为它参与了严重疟疾的病理生理过程，并促使了抗黏附疗法的发展，以破坏CD36-PE的相互作用。这一概念受到了出人意料的证据的挑战，这些证据表明，CD36基因缺陷的人更容易患上严重的脑型疟疾。在这项研究中，我们证明CD36是介导巨噬细胞对PE的非调理吞噬作用的主要受体，这是一种对严重疟疾风险最大的非免疫宿主具有潜在重要性的清除机制。CD36介导的PES摄取是通过一种新的途径发生的，该途径不涉及凝血酶敏感蛋白、玻璃体连接素受体或磷脂酰丝氨酸识别。此外，我们还发现，增殖物激活受体γ-维甲酸X受体激动剂可诱导CD36介导的吞噬功能增加，并减少寄生虫诱导的肿瘤坏死因子-α的分泌。单核/巨噬细胞CD36的特异性上调可能代表了一种预防或治疗严重疟疾的新的治疗策略。
Severe and fatal malaria is associated with the failure of host defenses to control parasite replication, excessive secretion of proinflammatory cytokines such as TNF-alpha and sequestration of parasitized erythrocytes (PEs) in vital organs. The identification of CD36 as a major sequestration receptor has led to the assumption that it contributes to the pathophysiology of severe malaria and has prompted the development of antiadherence therapies to disrupt the CD36-PE interaction. This concept has been challenged by unexpected evidence that individuals deficient in CD36 are more susceptible to severe and cerebral malaria. In this study, we demonstrate that CD36 is the major receptor mediating nonopsonic phagocytosis of PEs by macrophages, a clearance mechanism of potential importance in nonimmune hosts at the greatest risk of severe malaria. CD36-mediated uptake of PES occurs via a novel pathway that does not involve thrombospondin, the vitronectin receptor, or phosphatidylserine recognition. Furthermore, we show that proliferator-activated receptor gamma -retinoid X receptor agonists induce an increase in CD36-mediated phagocytosis and a decrease in parasite-induced TNF-a secretion. Specific up-regulation of monocyte/macrophage CD36 may represent a novel therapeutic strategy to prevent or treat severe malaria.