Intravital observation of Plasmodium berghei sporozoite infection of the liver.
Intravital observation of Plasmodium berghei sporozoite infection of the liver.
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DOI：
10.1371/journal.pbio.0030192
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发表时间：
2005-06
期刊：
影响因子：
9.8
通讯作者：
Yee H
中科院分区：
文献类型：
--
作者：
Frevert U;Engelmann S;Zougbédé S;Stange J;Ng B;Matuschewski K;Liebes L;Yee H
疟原虫子孢子侵入肝细胞一直是一个非常难以捉摸的事件。在流行的模型中，子孢子通过库普弗细胞进入肝脏，但该模型仅基于对固定标本的偶然观察以及生化和生理数据。为了获得有关肝子孢子感染动态的直接信息，我们用红色或绿色荧光伯氏疟原虫子孢子感染活鼠，并用活体显微镜监测它们的行为。数字记录显示，进入肝小叶的子孢子突然附着在肝窦细胞层上，表明存在高亲和力的相互作用。它们沿着正弦滑动，与血流一起或逆着血流，到达库普弗细胞，通过缓慢地推动收缩，穿过迪斯的空间。一旦进入肝实质，子孢子迅速移动许多分钟，穿过几个肝细胞，直到最终在最后一个肝细胞内稳定下来。在肝脏切片中证实了对肝细胞的移行性损伤，显示出与结构完整的、子孢子感染的肝细胞相邻的坏死性肝细胞簇，以及血清丙氨酸转氨酶活性的升高。总而言之，疟疾子孢子与血窦细胞层紧密结合，穿过库普弗细胞，在迁移到肝脏的最终目的地时留下一系列死亡的肝细胞。疟原虫属的微小寄生虫引起疟疾。通过使用活体显微镜观察寄生虫对肝脏的渗透，发现了寄生虫生活史的新细节。
Plasmodium sporozoite invasion of liver cells has been an extremely elusive event to study. In the prevailing model, sporozoites enter the liver by passing through Kupffer cells, but this model was based solely on incidental observations in fixed specimens and on biochemical and physiological data. To obtain direct information on the dynamics of sporozoite infection of the liver, we infected live mice with red or green fluorescent Plasmodium berghei sporozoites and monitored their behavior using intravital microscopy. Digital recordings show that sporozoites entering a liver lobule abruptly adhere to the sinusoidal cell layer, suggesting a high-affinity interaction. They glide along the sinusoid, with or against the bloodstream, to a Kupffer cell, and, by slowly pushing through a constriction, traverse across the space of Disse. Once inside the liver parenchyma, sporozoites move rapidly for many minutes, traversing several hepatocytes, until ultimately settling within a final one. Migration damage to hepatocytes was confirmed in liver sections, revealing clusters of necrotic hepatocytes adjacent to structurally intact, sporozoite-infected hepatocytes, and by elevated serum alanine aminotransferase activity. In summary, malaria sporozoites bind tightly to the sinusoidal cell layer, cross Kupffer cells, and leave behind a trail of dead hepatocytes when migrating to their final destination in the liver. Tiny parasites of the Plasmodium genus cause malaria. New details of the parasites' life cycle are uncovered through the use of intravital microscopy to observe the parasites' infiltration of the liver.
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