ICAM-1-binding Plasmodium falciparum erythrocyte membrane protein 1 variants elicits opsonic-phagocytosis IgG responses in Beninese children

Members of the highly polymorphic Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) family expressed on the surface of infected erythrocytes (IEs) are important virulence factors, which mediate vascular adhesion of IEs via endothelial host receptors and are targets of naturally acquired immunity. The PfEMP1 family can be divided into clinically relevant subgroups, of which some bind intercellular adhesion molecule 1 (ICAM-1). While the acquisition of IgG specific for ICAM-1-binding DBL beta domains is known to differ between PfEMP1 groups, its ability to induce antibody-dependent cellular phagocytosis (ADCP) is unclear. We therefore measured plasma levels of DBL beta-specific IgG, the ability of such IgG to inhibit PfEMP1-binding to ICAM-1, and its ability to opsonize IEs for ADCP, using plasma from Beninese children with severe (SM) or uncomplicated malaria (UM). IgG specific for DBL beta from group A and B ICAM-1-binding PfEMP1 were dominated by IgG1 and IgG3, and were similar in SM and UM. However, levels of plasma IgG inhibiting ICAM-1-binding of group A DBL beta of PFD1235w was significantly higher in children with UM than SM, and acute UM plasma induced a higher ADCP response than acute SM plasma.

Automated summary

The highly polymorphic Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) family is expressed on the surface of infected erythrocytes and is crucial for the virulence of malaria. This study found that different clinically relevant subgroups of PfEMP1 exhibit varying levels of binding to ICAM-1, with higher levels of specific IgG against ICAM-1-binding DBL beta domains in uncomplicated malaria (UM) children. Additionally, plasma from UM children elicited a stronger antibody-dependent cellular phagocytosis (ADCP) response compared to plasma from severe malaria (SM) children.