Understanding evasion of the innate immune system by malaria parasites

Examining early splenic innate immune responses during Plasmodium parasite infection are the focus of intense studies as it been indicated to be essential in determining host infection outcome. The current information in this area showed that expression profile of different parasitic factors such as variant surface antigens, encoded by large multigene families, can have crucial immune evasion and modulatory interactions against individual innate immune cell subpopulations in vitro. This intricate relationship between the various splenic innate immune cells and the largest variant surface antigens family in Plasmodium however have been greatly understudied due to the challenges involved in obtaining a homogenous parasite population expressing a single member. In this proposal, we will utilize an established technical approach to overcome these challenges to study the biological roles of specifically defined Plasmodium interspersed repeats members across a range of Plasmodium species. We will focus our study on yirs in P. yoelii, the rodent malaria infection model, and kirs in P. knowlesi, the zoonotic parasite causing significant human morbidity in Southeast Asia. Understanding the interplay between the host innate immune responses and the parasitic factors involved will not only deepen our understanding of Plasmodium pathogenesis, but it will also directly contribute to novel intervention strategies and possibly better clinical management against P. vivax, P. knowlsei, and other potential zoonotic infections in humans.