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-1 alpha 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.