In vitro development of infectious liver stages of P. yoelii and P. berghei malaria in human cell lines.

The preerythrocytic stages of the malaria parasite are the focus of intense efforts to identify new immunological and pharmacological methods for the control of the malaria parasite. The study of the malaria hepatic stages requires an in vitro system to facilitate the analysis of parasite/host cell interactions and the characterization of exoerythrocytic form (EEF) antigens. At the present time, only the rodent malaria, Plasmodium berghei, and the human malaria, Plasmodium vivax, develop into mature infectious EEF within established cell lines in vitro. We therefore used the rodent malaria, Plasmodium yoelii, which lacks a cell line for in vitro cultivation of EEF, to screen a series of human cell lines as potential host cells for the intracellular stage of the malaria parasite. Two human hepatomas, huH-1 and huH-2, were identified that supported the development of P. yoelii EEF which were antigenically and morphologically mature. Infectious merozoites that were shown to be capable of inducing P. yoelii blood infections in vivo developed within these in vitro EEF. In addition, mature, infectious EEF of P. berghei, but not P. yoelii, were found to develop within human HeLa cells. Preliminary results suggest that the cell lines that support the intracellular growth of P. yoelii might also serve as host cells for EEF of Plasmodium falciparum. The identification and characterization of the unique intracellular requirements for differentiation and development of P. berghei and P. yoelii EEF may provide new approaches to the prophylaxis of the human malaria species.