Interaction of PfEMP1 and Neutrophil ICAM-1 drives strong selection against Plasmodium falciparum subpopulation that causes severe malaria

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. Here we show 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. In addition, we identified neutrophil ICAM-1, as an essential receptor for their interaction with iRBCs and their ability to kill Plasmodium parasites. Our data provide mechanistic insight into the interaction between neutrophils and iRBCs demonstrating their important role in the innate immune response against malaria.