Host cell signalling and programmed cell death in Plasmodium liver stage prasites CLUSTER: "Parasite-host coevolution of programmed cell death"

疟原虫肝期寄生虫中的宿主细胞信号传导和程序性细胞死亡集群：“程序性细胞死亡的寄生虫-宿主共同进化”

• 批准号: 131727288
• 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: 2009
• 资助国家: 德国
• 起止时间: 2008-12-31 至 2013-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/131727288?language=en
• 关键词: Host; cell; signalling; programmed; death

There is clear evidence that Plasmodium parasites undergo a kind of programmed cell death (PCD). However, little is known about the molecular mechanisms that are responsible for such an event. Intracellular liver stage Plasmodium parasites are known to modulate PCD of their host cells but now it appears that MAP kinase signalling in the host cell interacts with parasite MAP kinase signalling to support survival of the pathogen. To analyse the molecular basis of PCD in Plasmodium, database searches for molecules involved in both apoptosis and autophagy, the two most common types of PCD, have been conducted on several Plasmodium species. Interestingly, the predicted proteomes of these parasites were found to lack molecules responsible for apoptosis, whereas proteins responsible for autophagic processes were identified. Plasmodium parasites undergo several dramatic reorganisations during their life cycle and it is plausible that they employ autophagy as a means to remove dispensable cellular material. It is reasonable to assume that during evolution, autophagy was additionally used to eliminate excess parasites or parasites that have not successfully entered a host cell, to avoid provoking strong inflammatory immune responses.

有明确的证据表明，疟原虫寄生虫经历一种程序性细胞死亡（PCD）。然而，很少有人知道的分子机制，负责这样的事件。已知细胞内肝期疟原虫寄生虫调节其宿主细胞的PCD，但现在看来宿主细胞中的MAP激酶信号传导与寄生虫MAP激酶信号传导相互作用以支持病原体的存活。为了分析疟原虫中PCD的分子基础，对几种疟原虫物种进行了细胞凋亡和自噬（两种最常见的PCD类型）中所涉及的分子的数据库搜索。有趣的是，这些寄生虫的预测蛋白质组被发现缺乏负责细胞凋亡的分子，而负责自噬过程的蛋白质被确定。疟原虫寄生虫在其生命周期中经历了几次戏剧性的重组，并且似乎它们采用自噬作为去除细胞物质的手段。可以合理地假设，在进化过程中，自噬还被用于消除多余的寄生虫或未成功进入宿主细胞的寄生虫，以避免引起强烈的炎症免疫反应。