Deciphering host lysosome-mediated elimination of Plasmodium berghei liver stage parasites
Deciphering host lysosome-mediated elimination of Plasmodium berghei liver stage parasites
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DOI：
10.1038/s41598-019-44449-z
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发表时间：
2019-05-28
影响因子：
4.6
通讯作者：
Heussler, V. T.
中科院分区：
文献类型：
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作者：
Niklaus, L.;Agop-Nersesian, C.;Heussler, V. T.
肝期疟原虫寄生在与溶酶体相关的寄生虫空泡（PV）中。以前已经表明，这些细胞器可以对寄生虫产生有益和有害的影响。然而，目前尚不清楚溶酶体与寄生虫的关联是如何控制的，以及与这些细胞器的相互作用如何导致拮抗结果。在这项研究中，我们使用先进的成像技术来表征溶酶体与PV的相互作用。在宿主细胞窝藏成功发展的寄生虫，我们观察到，这些相互作用的事件达到平衡的PV膜（PVM）。在一个人口逮捕寄生虫，这种平衡似乎转向强烈增加的溶酶体融合与PVM见证了强PVM标记与溶酶体标志物蛋白LAMP 1。随后是PV的酸化和寄生虫的消除。为了系统地研究消除被捕的寄生虫，我们产生了表达光敏剂KillerRed的转基因寄生虫，其在激活后导致寄生虫杀死。我们的工作提供了见解的细胞内杀死和溶酶体消除疟原虫寄生虫的免疫系统细胞的细胞细节。
Liver stage Plasmodium parasites reside in a parasitophorous vacuole (PV) that associates with lysosomes. It has previously been shown that these organelles can have beneficial as well as harmful effects on the parasite. Yet it is not clear how the association of lysosomes with the parasite is controlled and how interactions with these organelles lead to the antagonistic outcomes. In this study we used advanced imaging techniques to characterize lysosomal interactions with the PV. In host cells harboring successfully developing parasites we observed that these interaction events reach an equilibrium at the PV membrane (PVM). In a population of arrested parasites, this equilibrium appeared to shift towards a strongly increased lysosomal fusion with the PVM witnessed by strong PVM labeling with the lysosomal marker protein LAMP1. This was followed by acidification of the PV and elimination of the parasite. To systematically investigate elimination of arrested parasites, we generated transgenic parasites that express the photosensitizer KillerRed, which leads to parasite killing after activation. Our work provides insights in cellular details of intracellular killing and lysosomal elimination of Plasmodium parasites independent of cells of the immune system.