Hviid Lars, Jensen Anja T R
Centre for Medical Parasitology, University of Copenhagen and Copenhagen University Hospital (Rigshospitalet), Copenhagen, Denmark.
Adv Parasitol. 2015 Apr;88:51-84. doi: 10.1016/bs.apar.2015.02.004. Epub 2015 Mar 23.
Plasmodium falciparum causes the most severe form of malaria and is responsible for essentially all malaria-related deaths. The accumulation in various tissues of erythrocytes infected by mature P. falciparum parasites can lead to circulatory disturbances and inflammation, and is thought to be a central element in the pathogenesis of the disease. It is mediated by the interaction of parasite ligands on the erythrocyte surface and a range of host receptor molecules in many organs and tissues. Among several proteins and protein families implicated in this process, the P. falciparum erythrocyte membrane protein 1 (PfEMP1) family of high-molecular weight and highly variable antigens appears to be the most prominent. In this chapter, we aim to provide a systematic overview of the current knowledge about these proteins, their structure, their function, how they are presented on the erythrocyte surface, and how the var genes encoding them are regulated. The role of PfEMP1 in the pathogenesis of malaria, PfEMP1-specific immune responses, and the prospect of PfEMP1-specific vaccination against malaria are also covered briefly.
恶性疟原虫导致最严重形式的疟疾,基本上所有与疟疾相关的死亡都由其引起。成熟的恶性疟原虫寄生虫感染的红细胞在各种组织中的积聚可导致循环系统紊乱和炎症,并且被认为是该疾病发病机制的核心要素。它是由红细胞表面的寄生虫配体与许多器官和组织中的一系列宿主受体分子之间的相互作用介导的。在与此过程相关的几种蛋白质和蛋白质家族中,高分子量且高度可变的抗原——恶性疟原虫红细胞膜蛋白1(PfEMP1)家族似乎最为突出。在本章中,我们旨在系统概述关于这些蛋白质的现有知识、它们的结构、功能、它们如何呈现在红细胞表面以及编码它们的var基因是如何被调控的。还简要介绍了PfEMP1在疟疾发病机制中的作用、PfEMP1特异性免疫反应以及针对疟疾的PfEMP1特异性疫苗接种的前景。