We study the immune response to the malaria parasite, and are interested in those components involved in protection from infection, and those contributing to the pathology of malaria, as well as the parasite molecules that stimulate these responses.
We use a mouse model of malaria Plasmodium chabaudi to dissect mechanisms of immunity, pathogenesis and parasite virulence. We have recently shown that virulence of infection is attenuated by transmission through the mosquito vector. This attenuation appears to be the result of an altered interaction of mosquito-transmitted parasites with the host immune system early in a blood-stage infection, and is associated with increased expression of members of a parasite multigene family of variant proteins, cir.
As yet we do not know whether CIR proteins are directly responsible for attenuation of blood-stage malaria infections and whether they are targets of protective immunity. Long-lived protective immunity to blood-stage malaria does develop in our experimental model.
We are investigating the CD4 T cell and B-cell responses required to produce and regulate this response. CD4 T cells are key players. IL-10-producing CD4 T cells control the inflammatory response that is important for the pathology of malaria. The B-cell and antibody response necessary to eliminate chronic infection is critically dependent on the CD4 T-cell cytokine, IL-21.
We are also part of a large consortium investigating the immune response of children to the human parasite Plasmodium falciparum using a systems immunology approach to determine immune signatures of children who suffer from repeated episodes of febrile malaria before eventually developing clinical immunity. Our particular interest is the CD4 T-cell response and the association of different functional subsets with protective immunity or pathology.
Figure 1: Many genes up-regulated in mosquito-transmitted Plasmodium chabaudi parasites compared with direct blood passage: majority belong to the pir/cir multigene family (from Spence et al 2013, Nature, 498228-31). (Click to view larger image)