Adaptive NK cells in people exposed to Plasmodium falciparum correlate with protection from malaria

Geoffrey T. Hart, Tuan M. Tran, Jakob Theorell, Heinrich Schlums, Gunjan Arora, Sumati Rajagopalan, A. D. Jules Sangala, Kerry J. Welsh, Boubacar Traore, Susan K. Pierce, Peter D. Crompton, Yenan T. Bryceson, Eric O. Long

Research output: Contribution to journalArticlepeer-review

23 Scopus citations


How antibodies naturally acquired during Plasmodium falciparum infection provide clinical immunity to blood-stage malaria is unclear. We studied the function of natural killer (NK) cells in people living in a malaria-endemic region of Mali. Multiparameter flow cytometry revealed a high proportion of adaptive NK cells, which are defined by the loss of transcription factor PLZF and Fc receptor γ-chain. Adaptive NK cells dominated antibody-dependent cellular cytotoxicity responses, and their frequency within total NK cells correlated with lower parasitemia and resistance to malaria. P. falciparum–infected RBCs induced NK cell degranulation after addition of plasma from malaria-resistant individuals. Malaria-susceptible subjects with the largest increase in PLZF-negative NK cells during the transmission season had improved odds of resistance during the subsequent season. Thus, antibody-dependent lysis of P. falciparum–infected RBCs by NK cells may be a mechanism of acquired immunity to malaria. Consideration of antibody-dependent NK cell responses to P. falciparum antigens is therefore warranted in the design of malaria vaccines.

Original languageEnglish (US)
Pages (from-to)1280-1290
Number of pages11
JournalJournal of Experimental Medicine
Issue number6
StatePublished - Jun 1 2019

Bibliographical note

Funding Information:
The study was funded by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, AI000525-30 LIG (E.O. Long) and AI001155-06 LIG (P.D. Crompton). The authors declare no competing financial interests.

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