ABO Blood Group Antigen Decorated Giant Unilamellar Vesicles Exhibit Distinct Interactions with Plasmodium falciparum Infected Red Blood Cells

Abstract

Severe malaria is considered to be the deadliest disease of this century, primarily among children in sub-Saharan Africa. It stems from infection by the virulent parasite Plasmodium falciparum. The pathogenesis of the disease is based on the rosetting phenomenon, which occurs during the life cycle of the parasite in red blood cells (RBCs) and promotes the binding of parasitized RBCs to healthy ones. The role of the ABO blood group antigens in relation to the phenomenon has previously only been investigated in clinical isolates obtained from malaria patients. Here, we aim to clarify their role using synthetic ABO-decorated giant unilamellar vesicles (GUVs), which serve as simple biomimetic models of RBC-size cell membranes. Our results suggest clearly and for the first time that the blood group A and O antigens have a direct impact on receptor-specific rosetting phenomena when compared to the B antigen, which only participates in rosetting to an insignificant degree. Thus, glycodecorated GUVs represent a practical tool for studying cell-surface interactions.

Antiplasmodial Activity and In Vivo Bio-Distribution of Chloroquine Molecules Released with a 4-(4-Ethynylphenyl)-Triazole Moiety from Organometallo-Cobalamins

“…Given that the pathogenesis of the disease is based on the rosetting phenomenon [33], occurring during the life cycle of the P. falciparum in red blood cells (RBCs) promoting the binding of parasitized RBCs to healthy ones, our conceptual design pivots on the possibility that when attached to the cobalamin scaffold antimalarial drugs can be delivered to both erythrocytes and hepatocytes and intracellularly released following the natural Cbl pathway. We therefore needed to establish if the modified vitamins could still accumulate within red blood cells to some extent.…”

In vitro selection for adhesion of Plasmodium falciparum-infected erythrocytes to ABO antigens does not affect PfEMP1 and RIFIN expression

“…To our knowledge, selection for IE adhesion to ABO antigens in the absence of other potentially interfering receptors has not been reported before, but our results agree with reports implicating both blood group A and B antigens in rosetting 20 . The strong co-selection for IE adhesion to both A and B oligosaccharides by panning on either receptor indicates that the same parasite ligand(s) can bind both antigens, although this may not always be the case 42 . In addition to increased IE adhesion to BSA-A and BSA-B, selection on these receptors also lead to increased IE adhesion to several human cell lines (Fig.…”

Unveiling the Sugary Secrets of Plasmodium Parasites

“…These GPIs are recognized by macrophages and induce a proinflammatory, toxic response, thereby contributing to anemia. Barragan et al, 2000;Fry et al, 2008;Pathak et al, 2016;Vagianou et al, 2018 Frevert et al, 1993;Fry et al, 2008;Bushkin et al, 2010;Goel et al, 2015;Pathak et al, 2016;Kupferschmid et al, 2017;Vagianou et al, 2018 residues. The third mannose carries a phosphoethanolamine (PEtN) moiety that can covalently link the C-terminus of a protein to the GPI.…”

“…Blood group antigens A and B thus appear to be important co-receptors for rosette formation of infected RBCs. ABO-decorated giant unilamellar vesicles (GUVs) were used as RBC mimetics to examine rosette formation (Vagianou et al, 2018). A-and O-type GUVs participated in rosettes, but not B-type GUVs, and rosetting of O-type GUVs was inhibited with anti-Pf EMP1 Abs.…”