The liver is the first destination of malaria parasites in humans. After reaching the liver by the blood stream, Plasmodium sporozoites cross the liver sinusoid epithelium, enter and exit several hepatocytes, and eventually invade a final hepatocyte host cell. At present, the mechanism of hepatocyte invasion is only partially understood, presenting a key research gap with opportunities for the development of new therapeutics. Recently, human EphA2, a membrane-bound receptor tyrosine kinase, was implicated in hepatocyte infection by the human malaria parasite Plasmodium falciparum and the rodent parasite Plasmodium yoelii, but its role is not known for Plasmodium vivax, a major human parasite whose liver infection poses a specific challenge for malaria treatment and elimination. In this study, the role of EphA2 in P. vivax infection was investigated. It was found that surface expression of several recombinant fragments of EphA2 enhanced the parasite infection rate, thus establishing its role in P. vivax infection. Furthermore, a new permanent cell line (EphA2Extra-HC04) expressing the whole extracellular domain of EphA2 was generated. This cell line supports a higher rate of P. vivax infection and is a valuable tool for P. vivax liver-stage research.

肝脏是人类疟原虫的第一目的地。疟原虫子孢子经血流到达肝脏后，穿过肝窦上皮细胞，进出多个肝细胞，最终侵入最终的肝细胞宿主细胞。目前，肝细胞侵袭的机制仅得到部分了解，这为开发新疗法提供了一个关键的研究空白。最近，人类 EphA2（一种膜结合受体酪氨酸激酶）与人类疟疾寄生虫恶性疟原虫和啮齿动物寄生虫约氏疟原虫感染肝细胞有关，但其对间日疟原虫的作用尚不清楚，一种主要的人类寄生虫，其肝脏感染对疟疾治疗和消除提出了具体挑战。在这项研究中，研究了 EphA2 在间日疟原虫感染中的作用。发现 EphA2 的几个重组片段的表面表达提高了寄生虫感染率，从而确定了它在间日疟原虫感染中的作用。此外，产生了表达 EphA2 的整个细胞外结构域的新的永久性细胞系 (EphA2Extra-HC04)。该细胞系支持更高的间日疟原虫感染率，是间日疟原虫肝阶段研究的宝贵工具。