Department of Infection Biology, Faculty of Infectious Disease, London School of Hygiene & Tropical Medicine , London, United Kingdom.
mSphere. 2023 Oct 24;8(5):e0013123. doi: 10.1128/msphere.00131-23. Epub 2023 Aug 22.
Malaria parasites modify their host erythrocyte in multiple ways, leading to changes in the deformability, adhesiveness, and permeability of the host erythrocyte. Most of these changes are mediated by proteins exported from the parasite to the host erythrocyte, where these proteins interact with the host cell cytoskeleton or form complexes in the plasma membrane of the infected erythrocyte. In addition, malaria parasites induce the formation of membranous compartments-the parasitophorous vacuole, the tubovesicular network (TVN), the Maurer's clefts and small vesicles-within the infected erythrocyte, a cell that is normally devoid of internal membranes. After infection, changes also occur in the composition and asymmetry of the erythrocyte plasma membrane. Although many aspects of the mechanism of export of parasite proteins have become clear, the mechanism by which these membranous compartments are formed and expanded is almost entirely unknown. To determine whether parasite-derived phospholipids play a part in these processes, we applied a metabolic labeling technique that allows phosphatidylcholine to be labeled with a fluorophore. As the host erythrocyte cannot synthesize phospholipids, within infected erythrocytes, only parasite-derived phosphatidylcholine will be labeled with this technique. The results revealed that phosphatidylcholine produced by the parasite is distributed throughout the infected erythrocyte, including the TVN and the erythrocyte plasma membrane, but not Maurer's clefts. Interestingly, labeled phospholipids were also detected in the erythrocyte plasma membrane very soon after invasion of the parasites, indicating that the parasite may add phospholipids to the host erythrocyte during invasion. IMPORTANCE Here, we describe a previously unappreciated way in which the malaria parasite interacts with the host erythrocyte, namely, by the transfer of parasite phospholipids to the erythrocyte plasma membrane. This likely has important consequences for the survival of the parasite in the host cell and the host organism. We show that parasite-derived phospholipids are transferred from the parasite to the host erythrocyte plasma membrane and that other internal membranes that are produced after the parasite has invaded the cell are produced, at least in part, using parasite-derived phospholipids. The one exception to this is the Maurer's cleft, a membranous organelle that is involved in the transport of parasite proteins to the surface of the erythrocyte. This reveals that the Maurer's cleft is produced in a different manner than the other parasite-induced membranes. Overall, these findings provide a platform for the study of a new aspect of the host-parasite interaction.
疟原虫通过多种方式改变宿主红细胞，导致宿主红细胞的变形性、黏附性和通透性发生变化。这些变化大多是由寄生虫分泌到宿主红细胞中的蛋白质介导的，这些蛋白质与宿主细胞骨架相互作用或在感染红细胞的质膜中形成复合物。此外，疟原虫诱导形成膜性隔室——寄生泡、管状囊泡网络（TVN）、迈尔氏裂隙和小囊泡——在感染的红细胞内，而正常情况下红细胞内没有内膜。感染后，红细胞质膜的组成和不对称性也会发生变化。尽管寄生虫蛋白外排的许多机制已经很清楚，但这些膜性隔室的形成和扩展的机制几乎完全未知。为了确定寄生虫衍生的磷脂是否参与这些过程，我们应用了一种代谢标记技术，该技术可以用荧光团标记磷脂酰胆碱。由于宿主红细胞不能合成磷脂，因此在用这种技术标记感染的红细胞时，只有寄生虫衍生的磷脂酰胆碱会被标记。结果表明，寄生虫产生的磷脂酰胆碱分布在整个感染的红细胞中，包括 TVN 和红细胞质膜，但不包括迈尔氏裂隙。有趣的是，在寄生虫入侵后不久，在红细胞质膜中也检测到了标记的磷脂，这表明寄生虫可能在入侵宿主红细胞时向其添加磷脂。重要性 在这里，我们描述了疟原虫与宿主红细胞相互作用的一种以前未被认识的方式，即寄生虫磷脂向红细胞质膜的转移。这对寄生虫在宿主细胞和宿主生物体中的存活可能具有重要意义。我们表明，寄生虫衍生的磷脂从寄生虫转移到宿主红细胞质膜，并且寄生虫入侵细胞后产生的其他内膜至少部分是使用寄生虫衍生的磷脂产生的。但迈尔氏裂隙除外，它是一种参与寄生虫蛋白向红细胞表面转运的膜性细胞器。这表明迈尔氏裂隙的形成方式与其他寄生虫诱导的膜不同。总的来说，这些发现为研究宿主-寄生虫相互作用的一个新方面提供了一个平台。
