Plasmodium knowlesi Ligand-receptor Process in Baboon (Papio anubis) Placenta

Abstract

Pregnancy associated malaria poses many risks to both women and their infants. It is characterized by the accumulation of infected erythrocytes in the intervillous spaces of the placenta leading to adverse reactions. Studies using the P. knowlesi-Olive baboon model of pregnancy malaria have demonstrated this phenomenon though the mechanisms and molecules involved are not known. This study sought to identify the ligands and receptor molecules that permit accumulation of infected erythrocytes in the placenta of P. knowlesi infected Olive baboons and to further test placental isolates for adhesion to purified receptors. Sequences of known Plasmodium erythrocyte binding antigens and human placental receptors were BLASTed against the genome of P. knowlesi and P. anubis respectively. Hits generated were analysed and characterized to determine the prospective ligands and receptors in P. knowlesi and P. anubis respectively. Also, four adult female baboons (P. anubis) were infected with P. knowlesi parasites and their placentas sampled. Infected erythrocytes isolated from these placentas were tested for binding against purified receptors. We identified Predicted CSPG 4 partial and Predicted HAPLN 1 as the putative receptor molecules in the Olive baboon. Further, the P. knowlesi erythrocyte binding proteins (EBP-alpha, EBP-beta and EBP-gamma) matched closely to the placental P. falciparum ligand Var2csa. However, static binding assays with P. knowlesi infected erythrocytes did not show any binding to purified receptors. This study has identified and proposed receptors and ligands involved in the adherence process in P. knowlesi infected Olive baboons during pregnancy.

Keywords: Plasmodium knowlesi, Olive baboon, receptor, ligand, malaria, pregnancy