Parasite species regulates T cell activation in human malaria

Plasmodium vivax offers unique challenges for malaria control and may prove a more difficult species to eradicate than Plasmodium falciparum. Yet compared to P. falciparum we know very little about the innate and adaptive immune responses that need to be harnessed to reduce disease and transmission. In this study, we inoculated human volunteers with a clonal field isolate of P. vivax and used systems immunology tools to track their response through infection and convalescence. Our data reveal Plasmodium vivax triggers an acute phase response that shares remarkable overlap with that of P. falciparum, suggesting a hardwired innate response that does not differentiate between parasite species. This leads to the global recruitment of innate-like and adaptive T cells into lymphoid tissues where up to one quarter of the T cell compartment is activated. Heterogeneous effector memory-like CD4+ T cells dominate this response and their activation coincides with collateral tissue damage. Remarkably, comparative transcriptional analyses show that P. falciparum drives even higher levels of T cell activation; diverging T cell responses may therefore explain why falciparum malaria more frequently causes severe disease.