Clearance of Plasmodium falciparum-infected red blood cells by NK cells and monocytes

Abstract

Abstract Antibodies naturally acquired during repeated exposure to the parasite Plasmodium falciparum are essential for control of blood-stage malaria. NK cells are innate immune cells with an important role in containing viral infections and tumor growth, mainly by direct cytotoxicity and inflammatory cytokine production. Recently, we reported that primary human NK cells lyse Plasmodium falciparum-infected red blood cells (iRBCs) via antibody-dependent cellular cytotoxicity (ADCC) in presence of IgG isolated from adults living in a malaria-endemic region. This NK-mediated lysis results in inhibition of parasite growth in vitro. Live imaging showed release of parasitophorous vacuoles (PV) from iRBCs after incubation with NK cells. Many of these PVs gave propidium iodide-positive signals, suggesting loss of viability of P. falciparum inside the PVs after NK-mediated iRBC lysis. I am interested to know whether and how PVs are eliminated and postulate that monocytes play a role in clearance of PVs, thereby reducing the inflammatory response. To observe the interaction of NK cells and monocytes with PVs, I isolated PVs from iRBCs by mild saponin treatment and mechanical disruption of RBC membranes. Purified PVs bind IgG isolated from adults living in a malaria-endemic region, showing that adults develop antibodies against Plasmodium antigens at the surface of PVs. Preliminary live imaging experiments show phagocytosis of PVs by monocytes. Currently I am testing the contribution of Fc receptors on monocytes to phagocytosis of PVs and the interaction of NK cells with PVs.