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

Gunjan AroraGeoffrey T HartJavier Manzella-LapeiraJustin Ya DoritchamouDavid L NarumL Michael ThomasJoseph BrzostowskiSumati RajagopalanOgobara K DoumboBoubacar TraoreLouis H MillerSusan K PiercePatrick Emmet DuffyPeter D CromptonSanjay Arvind DesaiXiaoxuan Zhuang
Published in: eLife (2018)
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.
Keyphrases
  • plasmodium falciparum
  • nk cells
  • red blood cell
  • endothelial cells
  • escherichia coli
  • hiv infected
  • induced pluripotent stem cells
  • dendritic cells
  • high throughput