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.
|Original language||English (US)|
|State||Published - Jun 26 2018|
Bibliographical noteFunding Information:
We thank AT Neal for P.f. 3D7 strain enriched for knobs, SA Arredondo for help with P.f. parasite culture, KW Deitsch for P.f. DC-J strain, A Lanzavecchia for Abs MGD21 and MGD21-LALA, and P.f. 3D7 strain enriched for RIFIN expression, B Hansen for scanning electron microscopy, L Lantz for IgG purification, J Skinner for statistics, and A Sajid for comments on the manuscript. National Institute of Allergy and Infectious Diseases Z01 AI000525-30 LIG Eric O Long The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
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