Summary Asymptomatic and obligatory liver stage (LS) infection of Plasmodium parasites presents an attractive target for antimalarial vaccine and drug development. Lack of robust cellular models to study LS infection has hindered the discovery and validation of host genes essential for intrahepatic parasite development. Here, we present a chemically differentiated mouse embryonic stem cell (ESC)-based LS model, which supports complete development of Plasmodium berghei exoerythrocytic forms (EEFs) and can be used to define new host-parasite interactions. Using our model, we established that host Pnpla2 , coding for adipose triglyceride lipase, is dispensable for P. berghei EEF development. In addition, we also evaluated in – vitro -differentiated human hepatocyte-like cells (iHLCs) to study LS of P. berghei and found it to be a sub-optimal infection model. Overall, our results present a new mouse ESC-based P. berghei LS infection model that can be utilized to study the impact of host genetic variation on parasite development. Highlights • MBA-differentiated mouse embryonic stem cells support P. berghei liver stages • Mouse Pnpla2 is dispensable for the P. berghei liver stage in vitro • P. berghei liver stages cannot mature in hepatocyte-like cells from human iPSCs Discovering new host-parasite interactions during the liver stage of malaria parasites remains crucial for the development of malaria intervention strategies. In this article, Tripathi and colleagues present a genetically tractable, mouse ESC-based malaria liver infection model which supports full development in vitro of a rodent malaria parasite. This opens up new ways of interrogating host-parasite interactions in varying host genetic backgrounds.
【저자키워드】 malaria, embryonic stem cells, hepatocyte-like cells, methoxybenzamide differentiation, Pnpla2,