PDF(Pubmed)
Abstract：
During co-evolution Plasmodium parasites and vertebrates went through a process of selection resulting in defined and preferred parasite-host combinations. As such, Plasmodium falciparum (Pf) sporozoites can infect human hepatocytes while seemingly incompatible with host cellular machinery of other species. The compatibility between parasite invasion ligands and their respective human hepatocyte receptors plays a key role in Pf host selectivity. However, it is unclear whether the ability of Pf sporozoites to mature in cross-species infection also plays a role in host tropism. Here we used fresh hepatocytes isolated from porcine livers to study permissiveness to Pf sporozoite invasion and development. We monitored intra-hepatic development via immunofluorescence using anti-HSP70, MSP1, EXP1, and EXP2 antibodies. Our data shows that Pf sporozoites can invade non-human hepatocytes and undergo partial maturation with a significant decrease in schizont numbers between day three and day five. A possible explanation is that Pf sporozoites fail to form a parasitophorous vacuolar membrane (PVM) during invasion. Indeed, the observed aberrant EXP1 and EXP2 staining supports the presence of an atypical PVM. Functions of the PVM include the transport of nutrients, export of waste, and offering a protective barrier against intracellular host effectors. Therefore, an atypical PVM likely results in deficiencies that may detrimentally impact parasite development at multiple levels. In summary, despite successful invasion of porcine hepatocytes, Pf development arrests at mid-stage, possibly due to an inability to mobilize critical nutrients across the PVM. These findings underscore the potential of a porcine liver model for understanding the importance of host factors required for Pf mid-liver stage development.
摘要：
在共同进化过程中，疟原虫寄生虫和脊椎动物经历了一个选择过程，导致确定和优选的寄生虫-宿主组合。因此，恶性疟原虫（Pf）子孢子可以感染人肝细胞，而似乎与其他物种的宿主细胞机制不相容。寄生虫侵袭配体与其各自人肝细胞受体之间的相容性在Pf宿主选择性中起关键作用。然而,目前尚不清楚Pf子孢子在跨物种感染中成熟的能力是否也在宿主嗜性中起作用。在这里，我们使用从猪肝中分离出的新鲜肝细胞来研究对Pf子孢子侵袭和发育的允许性。我们使用抗HSP70，MSP1，EXP1和EXP2抗体通过免疫荧光监测肝内发育。我们的数据表明，Pf子孢子可以侵入非人肝细胞并经历部分成熟，在第3天和第5天之间裂殖体数显着减少。可能的解释是Pf子孢子在入侵过程中无法形成寄生的液泡膜（PVM）。的确,观察到的异常EXP1和EXP2染色支持非典型PVM的存在。PVM的功能包括营养物质的运输，废物出口,并提供针对细胞内宿主效应物的保护性屏障。因此,非典型PVM可能导致缺陷,可能在多个水平上对寄生虫的发育产生不利影响.总之,尽管猪肝细胞成功入侵，亲民党发展在中期被捕，可能是由于无法在PVM中动员关键营养素。这些发现强调了猪肝脏模型对于理解Pf肝脏中期发育所需的宿主因子的重要性的潜力。
