Neutrophil Recognition and Immune Editing of P. falciparum Parasites

Plasmodium falciparum, the deadliest form of human malaria remains one of the major threats to human health in malaria endemic regions. While it is clear that the innate immune response plays an important role in P. falciparum infection, very little is known on the role of neutrophils in malaria. Our research shows that neutrophils, the most abundant white blood cells in the human circulation, interact with infected red blood cells (iRBC) and eliminate intra-erythrocytic stages in several parasite isolates. We found that expression of PfEMP1, the major variable surface protein expressed by the parasite, triggers a neutrophil immune reaction, leading to parasite clearance. Moreover, we identified significant changes in parasite PfEMP1 expression following interaction with neutrophils, suggesting that neutrophils induce parasite antigenic shifting in a yet unknown mechanism. In addition, we identified neutrophil ICAM1, as an essential receptor for their interaction with iRBCs and their ability to kill Plasmodium parasites. We show that parasite clearance is mediated by neutrophil’s oxidative burst, as blocking this process significantly diminishes parasite death. Our data provide mechanistic insight into the interaction between neutrophils and iRBCs demonstrating their important role in the innate immune response against malaria.