Discussion

Plasmodium sporozoites are deposited in the host skin by a female Anopheles mosquito and migrate from the dermis to the liver parenchyma in order to infect hepatocytes, where they develop into replicative liver stages inside a parasitophorous vacuole. Sporozoites represent attractive targets for antimalarial preventive strategies, yet the mechanisms of parasite entry into hepatocytes remain poorly understood. We discovered that the two main species causing malaria in humans, P. falciparum and P. vivax, rely on two distinct host cell surface proteins to infect hepatocytes. Similarly, rodent-infecting P. yoelii and P. berghei sporozoites rely on distinct host factors for invasion. Using a genetic approach, we have now identified a key sporozoite protein that determines the host cell entry pathway used by the parasite to invade hepatocytes. Our data establish a functional link between sporozoite and host cell entry factors potentially involved in ligand-receptor interactions. These exciting results open novel perspectives to elucidate the molecular mechanisms involved in sporozoite host cell entry during malaria liver infection.