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NK cells inhibit Plasmodium falciparum growth in red blood cells via antibody-dependent cellular cytotoxicity

机译:NK细胞通过抗体依赖性细胞毒作用抑制红细胞中的恶性疟原虫生长

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Antibodies acquired naturally through repeated exposure to Plasmodium falciparum are essential in the control of blood-stage malaria. Antibody-dependent functions may include neutralization of parasite–host interactions, complement activation, and activation of Fc receptor functions. A role of antibody-dependent cellular cytotoxicity (ADCC) by natural killer (NK) cells in protection from malaria has not been established. Here we show that IgG isolated from adults living in a malaria-endemic region activated ADCC by primary human NK cells, which lysed infected red blood cells (RBCs) and inhibited parasite growth in an in vitro assay for ADCC-dependent growth inhibition. RBC lysis by NK cells was highly selective for infected RBCs in a mixed culture with uninfected RBCs. Human antibodies to P. falciparum antigens PfEMP1 and RIFIN were sufficient to promote NK-dependent growth inhibition. As these results implicate acquired immunity through NK-mediated ADCC, antibody-based vaccines that target bloodstream parasites should consider this new mechanism of action.
机译:通过反复接触恶性疟原虫自然获得的抗体对于控制血液阶段的疟疾至关重要。抗体依赖性功能可能包括中和寄生虫与宿主的相互作用,补体激活和Fc受体功能激活。尚未确定自然杀伤(NK)细胞的抗体依赖性细胞毒性(ADCC)在预防疟疾中的作用。在这里,我们显示从生活在疟疾流行区的成年人中分离得到的IgG通过原代人NK细胞激活ADCC,后者裂解感染的红细胞(RBC)并在体外测定中抑制寄生虫生长,以实现ADCC依赖性生长抑制。在未感染的RBC的混合培养物中,NK细胞对RBC的裂解具有很高的选择性。抗恶性疟原虫抗原PfEMP1和RIFIN的人抗体足以促进NK依赖性生长抑制。由于这些结果暗示了通过NK介导的ADCC获得的免疫力,针对血流寄生虫的基于抗体的疫苗应考虑这种新的作用机制。

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