Survival strategies of Plasmodium berghei exoerythrocytic forms (EEF) in hepatocytes

伯氏疟原虫红细胞外型（EEF）在肝细胞中的生存策略

• 批准号: 5435108
• 负责人: Professor Dr. Volker Theo Heussler
• 金额: --
• 依托单位: Institut für Zellbiologie
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 2004
• 资助国家: 德国
• 起止时间: 2003-12-31 至 2009-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/5435108?language=en
• 关键词: Survival; strategies; Plasmodium; berghei; exoerythrocytic

Survival of intracellular parasites depends on their ability to circumvent apoptosis of the host cell. Using the rodent parasite Plasmodium berghei as a model system we investigate survival strategies of Plasmodium parasites in hepatocytes from entry of sporozoites to the release of merozoites. In course of our ongoing studies we could show that during the first two days of infection the parasite protects the host cell from apoptosis, where as it induces apoptosis on the third day upon formation of merozoites. It is planned to study parasite dependent regulation of pro- and anti-apoptotic host signalling pathways as well as the molecular events leading to the dramatic changes in the host cell during merogony. Another goal of this proposal is the characterisation of merozoite formation in hepatocytes. This part of the project is based on our observation that parasitised hepatic cells round off and float in the supernatant briefly before they undergo apoptosis. Floating infected cells can easily be separated from non-infected adherent cells offering for the first time the possibility to study liver-derived Plasmodium parasites in detail. The identification and specific inhibition of parasite proteins needed for merozoite survival is envisaged. Apart from a more gereal approach to identify those parasite proteins we will focus on parasite proteases which are involved in the destruction of host cell membranes during the release of merozoites from hepatocytes.

细胞内寄生虫的存活取决于它们规避宿主细胞凋亡的能力。使用啮齿动物寄生虫伯氏疟原虫作为模型系统，我们研究了肝细胞中疟原虫寄生虫从子孢子进入到裂殖子释放的生存策略。在我们正在进行的研究过程中，我们可以证明，在感染的前两天，寄生虫可以保护宿主细胞免于凋亡，而在裂殖子形成的第三天，它会诱导细胞凋亡。计划研究促凋亡和抗凋亡宿主信号通路的寄生虫依赖性调节，以及导致宿主细胞在生殖期发生巨大变化的分子事件。该提案的另一个目标是表征肝细胞中裂殖子形成的特征。该项目的这一部分是基于我们的观察，即寄生的肝细胞在发生凋亡之前会暂时变圆并漂浮在上清液中。漂浮的感染细胞可以很容易地与未感染的贴壁细胞分离，这首次为详细研究肝源性疟原虫寄生虫提供了可能性。设想鉴定和特异性抑制裂殖子生存所需的寄生虫蛋白。除了鉴定这些寄生虫蛋白的更通用的方法之外，我们将重点关注在肝细胞释放裂殖子过程中参与破坏宿主细胞膜的寄生虫蛋白酶。