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

Gunjan Arora, Geoffrey T. Hart, Javier Manzella-Lapeira, Justin Y.A. Doritchamou, David L. Narum, L. Michael Thomas, Joseph Brzostowski, Sumati Rajagopalan, Ogobara K. Doumbo, Boubacar Traore, Louis H. Miller, Susan K. Pierce, Patrick E. Duffy, Peter D. Crompton, Sanjay A. Desai, Eric O. Long

Research output: Contribution to journalArticlepeer-review

66 Scopus citations


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 languageEnglish (US)
Article numbere36806
StatePublished - Jun 26 2018

Bibliographical note

Funding 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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