MALARIA LIVER STAGE : HOST CELL AND PARASITE DETERMINANTS OF PLASMODIUM SPOROZOITE ENTRY INTO HEPATOCYTES

Orateur : Olivier SILVIE (CIMI, Paris)

Malaria begins with the inoculation of Plasmodium sporozoites into the host skin by infected Anopheles mosquitoes. Sporozoites rapidly migrate to the liver and actively invade hepatocytes, where they ifferentiate into thousands of pathogenic blood-infective merozoites. Infection of the liver is an essential, initial and clinically silent phase of the malaria life cycle, and therefore constitutes an ideal target for a malaria vaccine. However, until now the molecular interactions mediating Plasmodium sporozoite invasion have remained enigmatic. We have identified two hepatocyte surface proteins, the tetraspanin protein CD81 and the Scavenger Receptor BI (SR-BI), as important host entry factors for Plasmodium falciparum and Plasmodium vivax, respectively. Using genetic approaches and rodent malaria models, we uncovered the crucial role of parasite proteins belonging to the 6-cysteine domain family. For the first time, we could establish a functional link between sporozoite and host cell entry factors. These results open novel perspectives to elucidate the molecular interactions involved in sporozoite host cell entry, and to develop new prevention strategies against malaria liver infection.

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