Malaria remains one of the most severe parasitic infections of humans in the world. It is estimated that over 250 million people become infected with malaria each year, resulting in over 400,000 deaths, mainly of young children in Sub Saharan Africa, each year. Although the Plasmodium protozoan parasite was first shown to be the causative agent of malaria over 130 years ago, we still have a very poor understanding of why some individuals are susceptible to malaria infection and why others are resistant. This is in large part due to our lack of knowledge of the pathogenesis of the most severe complications of malaria infection, such as cerebral malaria. My group use murine models of malaria and employ a variety of novel and established in vivo, ex vivo and in vitro techniques to investigate the spatiotemporal parasitological and immunological processes that initiate and cause severe malarial disease. Delineating the pathways that cause severe malaria should directly facilitate the development of adjunct treatments that can be used in combination with anti-malarial drugs to ameliorate malarial disease.
We also use murine models of malaria to dissect how antigen-specific effector, regulatory and memory immune responses develop and self-regulate during malaria infection. Although generation of effector T cell responses is essential for the control and clearance of the malaria parasite during infection, we now know that failure to regulate the pro-inflammatory cascades can lead to severe tissue damage and pathology. Moreover, the continual susceptibility of indviduals living in malaria endemic regions is believed to be, in part, due to their inability to develop protective and durable memory T cell responses against the parasite. By dissociating the signals responsible for induction of pro-inflammatory, regulatory and memory immune responses during malaria infection we should be able to manipulate the immune response therapeutically to optimise the control and resolution of infection.