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

有明确证据表明，疟原虫经历了一种程序性细胞死亡（PCD）。然而，人们对导致这一事件的分子机制知之甚少。众所周知，细胞内肝期疟原虫可以调节宿主细胞的PCD，但现在看来，宿主细胞中的MAP激酶信号与寄生虫的MAP激酶信号相互作用，以支持病原体的存活。为了分析疟原虫PCD的分子基础，我们对几种疟原虫进行了数据库检索，寻找与凋亡和自噬相关的分子，这是两种最常见的PCD类型。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。疟原虫在其生命周期中经历了几次戏剧性的重组，它们利用自噬作为去除不必要的细胞物质的手段是合理的。我们有理由认为，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，以避免引发强烈的炎症免疫反应。

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.