Mavoungou Elie, Held Jana, Mewono Ludovic, Kremsner Peter G
Medical Research Unit, Albert Schweitzer Hospital, Lambarene, Gabon.
J Infect Dis. 2007 May 15;195(10):1521-31. doi: 10.1086/515579. Epub 2007 Apr 3.
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.
最近的研究表明，纯化的自然杀伤（NK）细胞可裂解恶性疟原虫寄生的红细胞（Pf-pRBCs），这表明先天免疫在疟疾中起着重要作用。NK细胞的杀伤作用——可能是宿主对感染的早期反应——需要NK自然细胞毒性受体（NCRs）与Pf-pRBCs表面表达的配体密切接触。我们研究了寄生红细胞上表达的恶性疟原虫红细胞膜蛋白1（PfEMP-1）的达菲结合样（DBL）-1α结构域是否使Pf-pRBCs易被NK细胞裂解。我们发现，使用NKp30-免疫球蛋白和NKp46-免疫球蛋白融合蛋白以及DBL-1α肽，NCRs参与了NK细胞与Pf-pRBCs的相互作用。这种相互作用是直接、特异性且功能性的，导致穿孔素产生和颗粒酶B释放。用DBL-1α肽预先处理NK细胞消除了这种相互作用和杀伤活性，表明DBL-1α与NCRs的相互作用是NK细胞杀死寄生虫的关键识别机制。
