Plasmodium falciparum is responsible for the majority of malaria-related morbidity and mortality in humans. Of great importance to malaria pathology is the ability of P. falciparum-infected erythrocytes (PfIEs) to adhere to vascular endothelia. To date, little is known about the kinetics and dynamics of the cytoadhesion process, which depends mainly on a highly diverse protein family, P. falciparum erythrocyte membrane protein 1 (PfEMP1).
PfEMP1, which is presented on the erythrocyte surface, allows PfIEs to bind to various endothelial cell receptors (ECRs), thus disappear from the peripheral circulation and by removal by the spleen. The PfEMP1 family is encoded by approximately 45-90 var genes per parasite genome. Expression of var genes is mutually exclusive in ring-stage parasites, such that only a single PfEMP1 variant ever present on the surface of trophozoite- or schizonts-stage PfIEs at any given time. PfEMP1s are concentrated in nanoscale, electron-dense protrusions of the plasma membrane of PfIEs called knobs. Different PfEMP1s have different binding properties to ECRs and are associated with different clinical outcomes. Several studies have shown that severe malaria is associated with the expression of specific PfEMP1 groups, which include PfEMP1s that contain a binding domain for the endothelial protein C receptor (EPCR). In contrast, infections dominated by CD36-binding parasites show mild disease courses. Interestingly, between 75%-85% of PfEMP1s in a parasite isolate possess a binding domain for CD36.