Radboudumc Center for Infectious Diseases, Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, The Netherlands.
Department of surgery, Radboud University Medical Center, Nijmegen, The Netherlands.
EMBO J. 2021 Mar 15;40(6):e106583. doi: 10.15252/embj.2020106583. Epub 2021 Jan 18.
Plasmodium falciparum (Pf) is a major cause of human malaria and is transmitted by infected Anopheles mosquitoes. The initial asymptomatic infection is characterized by parasite invasion of hepatocytes, followed by massive replication generating schizonts with blood-infective merozoites. Hepatocytes can be categorized by their zonal location and metabolic functions within a liver lobule. To understand specific host conditions that affect infectivity, we studied Pf parasite liver stage development in relation to the metabolic heterogeneity of fresh human hepatocytes. We found selective preference of different Pf strains for a minority of hepatocytes, which are characterized by the particular presence of glutamine synthetase (hGS). Schizont growth is significantly enhanced by hGS uptake early in development, showcasing a novel import system. In conclusion, Pf development is strongly determined by the differential metabolic status in hepatocyte subtypes. These findings underscore the importance of detailed understanding of hepatocyte host-Pf interactions and may delineate novel pathways for intervention strategies.
疟原虫（Pf）是人类疟疾的主要病因，由受感染的按蚊传播。最初无症状的感染特征是寄生虫侵入肝细胞，随后大量复制产生具有血感染性裂殖子的合胞体。肝细胞可以根据其在肝小叶中的区域位置和代谢功能进行分类。为了了解影响感染性的特定宿主条件，我们研究了 Pf 寄生虫在与新鲜人类肝细胞代谢异质性相关的肝脏阶段的发育。我们发现不同 Pf 株对少数肝细胞具有选择性偏好，这些肝细胞的特征是谷氨酰胺合成酶（hGS）的特殊存在。在早期发育过程中，hGS 的摄取显著增强了合胞体的生长，展示了一种新的输入系统。总之，Pf 的发育受到肝细胞亚型中不同代谢状态的强烈影响。这些发现强调了详细了解肝细胞与 Pf 相互作用的重要性，并可能为干预策略开辟新途径。
