The malaria sporozoite's journey into the liver

Perhaps the most challenging event of the malaria parasite's lifecycle is the sporozoite's journey to the hepatocyte. Because few parasites are injected by the mosquito, they must be efficiently and rapidly targeted to hepatocytes, where they will invade and develop into merozoites, the form of the parasite infective for red blood cells. Little is known about how sporozoites make their way to the liver and subsequently invade hepatocytes. Some evidence suggests that they are initially trapped by Kupffer cells and then transported to hepatocytes. Other findings support the hypothesis that sporozoites home to hepatocytes directly. We have found that the major surface protein of malaria sporozoites, the CS protein, binds to the basolateral domain of hepatocytes and, when injected intravenously into mice, is rapidly cleared from the circulation by the liver. Whether sporozoites are arrested in the liver by the same mechanisms as CS protein is not known, although preliminary data suggests this may be the case. Other sporozoite proteins are also likely to be involved in hepatocyte invasion. TRAP or SSP2, found on the parasite surface and in micronemes, binds to hepatocytes in a similar pattern as CS protein. There is evidence demonstrating its involvement in invasion, although it is not known whether it functions in the initial sequestration of the parasites by the liver or in subsequent invasion events.