Role of Chondroitin‐4‐Sulfate in Pregnancy‐Associated Malaria

Abstract

Publisher Summary Many pathogenic microorganisms use glycosaminoglycans (GAGs) as receptors for cell‐ or tissue‐specific invasion, causing infection. In the case of pregnancy‐associated malaria, Plasmodium falciparum ‐infected red blood cells (IRBCs) adhere in the placenta, leading to a number of clinical manifestations. A uniquely low‐sulfated extracellular chondroitin sulfate proteoglycan (CSPG) localized in the intervillous space of the placenta is the receptor for the IRBC adherence. Chondroitin‐4‐sulfate (C4S) chains of the CSPG specifically mediate the IRBC adherence, and the optimal IRBC binding involves a C4S dodecasaccharide motif comprising two 4‐sulfated and four nonsulfated disaccharides. The sulfate and hydroxyl groups at C‐4 of N ‐acetylgalactosamine (GalNAc) and the carboxyl group of uronic acid are critical for the IRBC adhesion, whereas the N ‐acetyl group of GalNAc is not involved. P. falciparum erythrocyte membrane protein‐1, a member of the parasite var gene family of proteins that is expressed on the surface of IRBCs, has been proposed as the ligand for IRBC adherence. In malaria endemic areas, pregnant women produce IRBC antiadhesion antibodies in a pregnancy stage‐specific manner, which protect against placental malaria.