Cytoadhesion of Plasmodium falciparum ring-stage-infected erythrocytes

A common pathological characteristic of Plasmodium folciparum infection is the cytoadhesion of mature-stage-infected erythrocytes (IE) to host endothe lium and syncytiotrophoblasts. Massive accumulation of IE in the brain micr ovasculature or placenta is strongly correlated with severe forms of malari a(1). Extensive binding of IE to placental chondroitin sulfate A (CSA) is a ssociated with physiopathology during pregnancy(2,3). The adhesive phenotyp e of IE correlates with the appearance of Plasmodium:falciparum erythrocyte membrane protein 1 (PfEMP1) at the erythrocyte surface (approximately 16 h after merozoite invasion), so that only early blood-stage (ring-stage) IE appear in the peripheral blood. Here, we describe results that challenge th e existing view of blood-stage IE biology by demonstrating the specific adh esion of IE, during the early ring-stage, to endothelial cell lines from th e brain and lung and to placental syncytiotrophoblasts. Later, during blood -stage development of these IE; trophozoites switch to an exclusively CSA c ytoadhesion phenotype. Therefore, adhesion to an individual endothelial cel l or syncytiotrophoblast may occur throughout the blood-stage cycle, indica ting the presence in malaria patients of noncirculating (cryptic) parasite subpopulations. We detected two previously unknown parasite proteins on the surface of ring-stage IE. These proteins disappear shortly after the start of PfEMP1-mediated adhesion.