A Duffy binding-like domain is involved in the NKp30-mediated recognition of Plasmodium falciparum-parasitized erythrocytes by natural killer cells.
The recent demonstration that purified natural killer (NK) cells lyse Plasmodium falciparum-parasitized red blood cells (Pf-pRBCs) suggests that innate immunity is important in malaria. NK cell killing--presumably an early host response to infection--requires intimate contact between NK natural cytotoxicity receptors (NCRs) and ligands expressed on the surface of Pf-pRBCs. We investigated whether the Duffy binding-like (DBL)-1 alpha domain of P. falciparum erythrocyte membrane protein-1 (PfEMP-1) expressed on parasitized erythrocytes rendered Pf-pRBCs susceptible to NK cell lysis. We showed that with NKp30-immunoglobulin and NKp46-immunoglobulin fusion proteins and DBL-1alpha peptides NCRs are involved in the NK cell-Pf-pRBC interaction. This interaction was direct, specific, and functional, leading to perforin production and granzyme B release. The prior treatment of NK cells with DBL-1 alpha peptides abolished both this interaction and killing activity, suggesting that DBL-1 alpha -NCRs interaction is the key recognition mechanism leading to parasite killing by NK cells.
Mavoungou
Elie
E
Medical Research Unit, Albert Schweitzer Hospital, Lambarene, Gabon. elie.mavoungou@uni-tuebingen.de
Held
Jana
J
Mewono
Ludovic
L
Kremsner
Peter G
PG
D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D004375:Duffy Blood-Group System / Q000276:immunology*; D004912:Erythrocytes / Q000276:immunology* / Q000469:parasitology*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D016778:Malaria, Falciparum / Q000276:immunology; D055628:Natural Cytotoxicity Triggering Receptor 3; D010963:Plasmodium falciparum / Q000472:pathogenicity*; D011971:Receptors, Immunologic / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000276:immunology
D015703:Antigens, CD; D004375:Duffy Blood-Group System; C431710:NCR3 protein, human; D055628:Natural Cytotoxicity Triggering Receptor 3; D011971:Receptors, Immunologic; D011993:Recombinant Fusion Proteins