Antibodies targeting the PfRH1 binding domain inhibit invasion of Plasmodium falciparum merozoites.
Invasion by the malaria merozoite depends on recognition of specific erythrocyte surface receptors by parasite ligands. Plasmodium falciparum uses multiple ligands, including at least two gene families, reticulocyte binding protein homologues (RBLs) and erythrocyte binding proteins/ligands (EBLs). The combination of different RBLs and EBLs expressed in a merozoite defines the invasion pathway utilized and could also play a role in parasite virulence. The binding regions of EBLs lie in a conserved cysteine-rich domain while the binding domain of RBL is still not well characterized. Here, we identify the erythrocyte binding region of the P. falciparum reticulocyte binding protein homologue 1 (PfRH1) and show that antibodies raised against the functional binding region efficiently inhibit invasion. In addition, we directly demonstrate that changes in the expression of RBLs can constitute an immune evasion mechanism of the malaria merozoite.
Gao
Xiaohong
X
Division of Genomics & Genetics, School of Biological Sciences, Nanyang Technological University, Singapore.
Yeo
Kim Pin
KP
Aw
Siqi Sharon
SS
Kuss
Claudia
C
Iyer
Jayasree K
JK
Genesan
Saraswathy
S
Rajamanonmani
Ravikumar
R
Lescar
Julien
J
Bozdech
Zbynek
Z
Preiser
Peter R
PR
D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood / Q000276:immunology*; D000953:Antigens, Protozoan / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D001665:Binding Sites; D019556:COS Cells; D015815:Cell Adhesion Molecules; D002522:Chlorocebus aethiops; D002942:Circular Dichroism; D004912:Erythrocytes / Q000378:metabolism / Q000469:parasitology; D005786:Gene Expression Regulation; D020868:Gene Silencing; D006790:Host-Parasite Interactions; D052940:Merozoites / Q000737:chemistry / Q000276:immunology*; D010963:Plasmodium falciparum / Q000472:pathogenicity* / Q000502:physiology*; D015800:Protozoan Proteins / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry
D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D015815:Cell Adhesion Molecules; C066001:Duffy antigen binding protein, Plasmodium; D015800:Protozoan Proteins; C503374:RH1 protein, Plasmodium falciparum; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins