The manipulation of the human immune response by the liver stages of the malaria parasite.

• Applicant: Dr. Stephan Meister
• Subject Area: Parasitology and Biology of Tropical Infectious Disease Pathogens
• Term: Funded in 2009
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 108891716

In malaria, Plasmodium falciparum sporozoites rapidly travel to the liver after being injected into the human host by the bite of an infected mosquito. There, they appear to suppress the immune and inflammatory response while undergoing several multiplication cycles, finally developing into thousands of erythrocyte-infective merozoites. While much effort has been invested into understanding the antigenic variation of malaria blood stage parasites, very little is known about the mechanisms governing the asymptomatic malaria parasite development in the liver. I will functionally characterize (a) mechanisms of host immune suppression and (b) the inhibition of apoptosis both of which may be achieved via the parasite circumsporozoite protein (CSP). I will also (c) comprehensively determine the liver stage transcriptional program of the parasite and host liver cells to identify other candidate parasite and host factors that play a role in host immune system modulation and parasite liver stage development. I expect to discover host and parasite factors that are key to achieving a sterilizing host immune response in malaria infection. In doing so, I hope to contribute to making novel malaria drugs or a working malaria vaccine attainable.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professorin Elizabeth Winzeler, Ph.D.