Plasmodium falciparum field isolates use complement receptor 1 (CR1) as a receptor for invasion of erythrocytes

Abstract

A majority of Plasmodium falciparum strains invade erythrocytes through interactions with sialic acid (SA) on glycophorins. However, we recently reported that complement receptor 1 (CR1) is a SA-independent invasion receptor of many laboratory strains of P. falciparum. To determine the role of CR1 in erythrocyte invasion among P. falciparum field isolates, we tested eight isolates obtained from children in Kenya. All the parasites examined were capable of invading in a SA-independent manner, and invasion of neuraminidase-treated erythrocytes was nearly completely blocked by anti-CR1 and soluble CR1 (sCR1). In addition, anti-CR1 and sCR1 partially inhibited invasion of intact erythrocytes in a majority of isolates tested. Sequencing of the hypervariable region of P. falciparum AMA-1 showed considerable diversity among all the isolates. These data demonstrate that CR1 mediates SA-independent erythrocyte invasion in P. falciparum field isolates.

Figure 1. AMA-1 C1 cluster sequences show diversity among field isolates

P. falciparum isolates SA005, SA154, SA162, SA222, SA250, JACS8-19, CM028, and CM033 were collected from children with malaria in western Kenya. JACS8-8 and JASC8-10 were cloned from JACS8-19 and included as controls, as well as the common laboratory strain 3D7. The genetic diversity among the isolates is illustrated by a phylogenetic tree showing interrelationships according to the percentage differences in amino acid sequences of the polymorphic AMA-1 C1 cluster. Multiple AMA-1 sequences were detected in SA162 and CM028 and two possible haplotypes were presented for each of these isolates.