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

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Abstract

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. Multi-parameter 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
JournalThe Journal of experimental medicine
Volume216
Issue number6
DOIs
StatePublished - Jun 3 2019

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Plasmodium falciparum
Natural Killer Cells
Malaria
Antibodies
Mali
Malaria Vaccines
Cell Degranulation
Parasitemia
Fc Receptors
Adaptive Immunity
Immunity
Flow Cytometry
Transcription Factors
Antigens

PubMed: MeSH publication types

  • Journal Article

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Adaptive NK cells in people exposed to Plasmodium falciparum correlate with protection from malaria. / Hart, Geoffrey T; Tran, Tuan M.; Theorell, Jakob; Schlums, Heinrich; Arora, Gunjan; Rajagopalan, Sumati; Sangala, A. D.Jules; Welsh, Kerry J.; Traore, Boubacar; Pierce, Susan K.; Crompton, Peter D.; Bryceson, Yenan T.; Long, Eric O.

In: The Journal of experimental medicine, Vol. 216, No. 6, 03.06.2019, p. 1280-1290.

Research output: Contribution to journalArticle

Hart, GT, Tran, TM, Theorell, J, Schlums, H, Arora, G, Rajagopalan, S, Sangala, ADJ, Welsh, KJ, Traore, B, Pierce, SK, Crompton, PD, Bryceson, YT & Long, EO 2019, 'Adaptive NK cells in people exposed to Plasmodium falciparum correlate with protection from malaria', The Journal of experimental medicine, vol. 216, no. 6, pp. 1280-1290. https://doi.org/10.1084/jem.20181681
Hart, Geoffrey T ; Tran, Tuan M. ; Theorell, Jakob ; Schlums, Heinrich ; Arora, Gunjan ; Rajagopalan, Sumati ; Sangala, A. D.Jules ; Welsh, Kerry J. ; Traore, Boubacar ; Pierce, Susan K. ; Crompton, Peter D. ; Bryceson, Yenan T. ; Long, Eric O. / Adaptive NK cells in people exposed to Plasmodium falciparum correlate with protection from malaria. In: The Journal of experimental medicine. 2019 ; Vol. 216, No. 6. pp. 1280-1290.
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