Plasmodium salvages cholesterol internalized by LDL and synthesized de novo in the liver
Plasmodium salvages cholesterol internalized by LDL and synthesized de novo in the liver
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DOI：
10.1111/j.1462-5822.2010.01555.x
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发表时间：
2011-04-01
影响因子：
3.4
通讯作者：
Coppens, Isabelle
中科院分区：
文献类型：
--
作者：
Labaied, Mehdi;Jayabalasingham, Bamini;Coppens, Isabelle
P>；我们之前的形态研究说明了甾醇与感染肝细胞的疟原虫之间的关系。因为疟疾寄生虫不能合成类固醇，它们必须从宿主中清除这些脂类。在这篇论文中，我们研究了肝内疟原虫的固醇来源/S，并评估了固醇在肝脏发育阶段中的重要性。我们发现，疟原虫不断地转移肝细胞中的胆固醇，直到裂殖子释放。从培养液中去除血浆脂蛋白可使肝裂殖子中的胆固醇含量降低70%，但这些寄生虫在动物中仍具有传染性。疟原虫挽救了被低密度脂蛋白内化的胆固醇，但宿主低密度脂蛋白受体的表达减少了70%，不影响肝脏阶段的负担。疟原虫还能够拦截肝细胞合成的胆固醇。药物阻断宿主角鲨烯合成酶或将该酶的表达下调80%，可使裂殖子的胆固醇含量减少两倍，而不会进一步影响寄生虫的发育。这些数据表明，一方面，疟疾寄生虫在肝细胞中的最佳发育对类固醇的需求适中，另一方面，它们可以通过利用来自肝细胞中替代来源的可获得的类固醇来保持适当的传染性，从而适应在胆固醇限制的条件下生存。
P>Our previous morphological studies illustrated the association of sterols with Plasmodium infecting hepatocytes. Because malaria parasites cannot synthesize sterols, they must scavenge these lipids from the host. In this paper, we have examined the source/s of sterols for intrahepatic Plasmodium and evaluated the importance of sterols for liver stage development. We show that Plasmodium continuously diverts cholesterol from hepatocytes until release of merozoites. Removal of plasma lipoproteins from the medium results in a 70% reduction of cholesterol content in hepatic merozoites but these parasites remain infectious in animals. Plasmodium salvages cholesterol that has been internalized by low-density lipoprotein but reduced expression of host low-density lipoprotein receptors by 70% does not influence liver stage burden. Plasmodium is also able to intercept cholesterol synthesized by hepatocytes. Pharmacological blockade of host squalene synthase or downregulation of the expression of this enzyme by 80% decreases by twofold the cholesterol content of merozoites without further impacting parasite development. These data enlighten that, on one hand, malaria parasites have moderate need of sterols for optimal development in hepatocytes and, on the other hand, they can adapt to survive in cholesterol-restrictive conditions by exploitation of accessible sterols derived from alternative sources in hepatocytes to maintain proper infectivity.