Erythrocyte Invasion Mechanisms of Plasmodium Falciparum Clinical Isolates from Ghanaian Children

Abstract

Clinical manifestations of Plasmodium falciparum infections are caused by invasion of erythrocytes by malaria parasites, a process mediated by multiple receptor-ligand interactions. Antibodies against some parasite ligands significantly inhibit parasite growth in vitro, demonstrating that these interactions may be good targets for the development of an effective blood stage vaccine. This study was aimed at investigating the erythrocyte receptors used by P. falciparum isolates in Ghana. P. falciparum field isolates were collected from children aged 2-6 years attending hospitals in three ecologically distinct zones in Ghana: Accra, Navrongo, and Kintampo. Erythrocyte invasion assays were performed on eighteen isolates to test the ability of the parasites to invade erythrocytes treated with neuraminidase, trypsin and chymotrypsin which selectively remove receptors from the erythrocyte cell surface. In addition, antibodies against two recently identified receptors, basigin (BSG) and complement receptor 1 (CR1) were used to determine the dependence of the isolates on these pathways. One to three assays were performed on each isolate. The majority of field isolates tested were capable of invading neuraminidase- treated erythrocytes with greater than 50% invasion efficiencies relative to untreated erythrocytes, suggesting that these field isolates have sialic acid (SA)-independent invasion phenotypes. Invasion efficiency in trypsin-and chymotrypsin-treated erythrocytes varied between 20 to 75% relative to untreated erythrocytes. In all field isolates tested, antibodies against CR1 significantly inhibited invasion of neuraminidase-treated erythrocytes. However, anti-BSG antibodies significantly inhibited invasion in both untreated and neuraminidase-treated erythrocytes to a similar extent. This may suggest that the interaction between basigin and its parasite ligand PfRh5 may be upstream of interactions involving glycophorins and CR1.