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 neuraminidasetreated

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.