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 journalArticle

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Abstract

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
JournaleLife
Volume7
DOIs
StatePublished - Jun 26 2018

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Plasmodium falciparum
Cytotoxicity
Natural Killer Cells
Blood
Erythrocytes
Cells
Antibodies
Growth
Malaria
Parasites
Chemical activation
Cytoprotection
Fc Receptors
Complement Activation
Adaptive Immunity
Assays
Vaccines
Immunoglobulin G
Antigens

Cite this

Arora, G., Hart, G. T., Manzella-Lapeira, J., Doritchamou, J. Y. A., Narum, D. L., Thomas, L. M., ... Long, E. O. (2018). NK cells inhibit plasmodium falciparum growth in red blood cells via antibody-dependent cellular cytotoxicity. eLife, 7, [e36806]. https://doi.org/10.7554/eLife.36806

NK cells inhibit plasmodium falciparum growth in red blood cells via antibody-dependent cellular cytotoxicity. / Arora, Gunjan; Hart, Geoffrey T; Manzella-Lapeira, Javier; Doritchamou, Justin Y.A.; Narum, David L.; Thomas, L. Michael; Brzostowski, Joseph; Rajagopalan, Sumati; Doumbo, Ogobara K.; Traore, Boubacar; Miller, Louis H.; Pierce, Susan K.; Duffy, Patrick E.; Crompton, Peter D.; Desai, Sanjay A.; Long, Eric O.

In: eLife, Vol. 7, e36806, 26.06.2018.

Research output: Contribution to journalArticle

Arora, G, Hart, GT, Manzella-Lapeira, J, Doritchamou, JYA, Narum, DL, Thomas, LM, Brzostowski, J, Rajagopalan, S, Doumbo, OK, Traore, B, Miller, LH, Pierce, SK, Duffy, PE, Crompton, PD, Desai, SA & Long, EO 2018, 'NK cells inhibit plasmodium falciparum growth in red blood cells via antibody-dependent cellular cytotoxicity', eLife, vol. 7, e36806. https://doi.org/10.7554/eLife.36806
Arora, Gunjan ; Hart, Geoffrey T ; Manzella-Lapeira, Javier ; Doritchamou, Justin Y.A. ; Narum, David L. ; Thomas, L. Michael ; Brzostowski, Joseph ; Rajagopalan, Sumati ; Doumbo, Ogobara K. ; Traore, Boubacar ; Miller, Louis H. ; Pierce, Susan K. ; Duffy, Patrick E. ; Crompton, Peter D. ; Desai, Sanjay A. ; Long, Eric O. / NK cells inhibit plasmodium falciparum growth in red blood cells via antibody-dependent cellular cytotoxicity. In: eLife. 2018 ; Vol. 7.
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