In my laboratory we study the sporozoite stage of Plasmodium, the causative agent of malaria. During the bloodmeal of an infected Anopheline mosquito, Plasmodium sporozoites are injected into the vertebrate host, make their way to the bloodstream and then go to the liver where they invade hepatocytes. To date, little is known about the biology of sporozoites at the injection site. Using real time PCR and confocal microscopy, we are beginning to investigate what happens to sporozoites before they enter the bloodstream, how long they remain in the skin, what percentage of injected parasites leave the injection site and whether there is an immune response to the parasites that remain in the skin.
After their entry into the bloodstream, sporozoites rapidly go the liver and invade hepatocytes. The basis of sporozoite arrest in the liver is likely the binding between its major surface protein, the circumsporozoite protein (CSP) and heparan sulfate proteoglycans (HSPGs) on the hepatocyte surface. Previous work in our laboratory has characterized both the sporozoite ligand and the hepatic binding sites. Recently, we have found the CSP is proteolytically processed and that this processing is required for hepatocyte invasion. We are now investigating the role of HSPGs in inducing proteolytic cleavage of CSP, the identity of the protease that cleaves CSP, and the effect of protease inhibition in prevention of malaria infection.