title: PfRH2b specific monoclonal antibodies inhibit merozoite invasion.
abstract: Erythrocyte invasion by merozoite is a multistep process involving multiple ligand-receptor interactions. The Plasmodium falciparum reticulocyte binding protein homologues (PfRHs) consists of five functional members. The differential expression of PfRHs has been linked to the utilization of different invasion pathways by the merozoites as well as a mechanism of immune evasion. PfRHs are expressed at the apical end of merozoite and form interactions with distinct red blood cell (RBC) surface receptors that are important for successful invasion. Here we show that PfRH2b undergoes processing before and during merozoite invasion. The different processed fragments bind to chymotrypsin sensitive RBC surface receptors. We also show that PfRH2b follows the merozoite tight junction during invasion. Monoclonal antibodies (mAbs) inhibit merozoites invasion by blocking tight junction formation. mAbs binding to PfRH2b block merozoites intracellular Ca2+signal necessary for EBA175 surface expression. The data suggests that a conserved function of PfRHs, where their interaction with RBC surface receptors facilitated recruitment of EBA175 and other tight junction proteins necessary for merozoite invasion by modulating merozoite intracellular Ca2+signals.
authors.affiliation: Division of Molecular Genetics and Cell biology, School of Biological Sciences, Nanyang Technological University, 637551, Singapore.
authors.forename: Yaw
authors.initials: Y
authors.lastname: Aniweh
authors.affiliation: Division of Molecular Genetics and Cell biology, School of Biological Sciences, Nanyang Technological University, 637551, Singapore.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Gao
authors.affiliation: Division of Molecular Genetics and Cell biology, School of Biological Sciences, Nanyang Technological University, 637551, Singapore.
authors.forename: Karthigayan
authors.initials: K
authors.lastname: Gunalan
authors.affiliation: Division of Molecular Genetics and Cell biology, School of Biological Sciences, Nanyang Technological University, 637551, Singapore. PRPreiser@ntu.edu.sg.
authors.forename: Peter R
authors.initials: PR
authors.lastname: Preiser
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology*; D000918:Antibody Specificity; D002918:Chymotrypsin / Q000378:metabolism; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism / Q000469:parasitology*; D006790:Host-Parasite Interactions; D006801:Humans; D052940:Merozoites / Q000187:drug effects / Q000378:metabolism; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000378:metabolism*; D015800:Protozoan Proteins / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D015800:Protozoan Proteins; D011956:Receptors, Cell Surface; C545352:Rh2b protein, Plasmodium falciparum; D002918:Chymotrypsin