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Anti-merozoite antibodies induce natural killer cell effector function and are associated with immunity against malaria

Natural killer (NK) cells are potent immune effectors that can be activated via antibody-mediated Fc receptor engagement. Using multiparameter flow cytometry, we found that NK cells degranulate and release IFN-γ upon stimulation with antibody-opsonized Plasmodium falciparum merozoites. Antibody-depe...

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Main Authors: Odera, Dennis (Author) , Tuju, James (Author) , Mwai, Kennedy (Author) , Nkumama, Irene Nailain (Author) , Fürle, Kristin (Author) , Chege, Timothy (Author) , Kimathi, Rinter (Author) , Diehl, Stefan (Author) , Musasia, Fauzia K. (Author) , Rosenkranz, Micha (Author) , Njuguna, Patricia (Author) , Hamaluba, Mainga (Author) , Kapulu, Melissa C. (Author) , Frank, Roland (Author) , Osier, Faith (Author)
Format: Article (Journal)
Language:English
Published: 8 Feb 2023
In: Science translational medicine
Year: 2023, Volume: 15, Issue: 682, Pages: 1-14
ISSN:1946-6242
DOI:10.1126/scitranslmed.abn5993
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1126/scitranslmed.abn5993
Verlag, lizenzpflichtig, Volltext: https://www.science.org/doi/10.1126/scitranslmed.abn5993
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Author Notes:Dennis O. Odera, James Tuju, Kennedy Mwai, Irene N. Nkumama, Kristin Fürle, Timothy Chege, Rinter Kimathi, Stefan Diehl, Fauzia K. Musasia, Micha Rosenkranz, Patricia Njuguna, Mainga Hamaluba, Melissa C. Kapulu, Roland Frank, on behalf of the CHMI-SIKA Study Team, Faith H. A. Osier
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Summary:Natural killer (NK) cells are potent immune effectors that can be activated via antibody-mediated Fc receptor engagement. Using multiparameter flow cytometry, we found that NK cells degranulate and release IFN-γ upon stimulation with antibody-opsonized Plasmodium falciparum merozoites. Antibody-dependent NK (Ab-NK) activity was largely strain transcending and enhanced invasion inhibition into erythrocytes. Ab-NK was associated with the successful control of parasitemia after experimental malaria challenge in African adults. In an independent cohort study in children, Ab-NK increased with age, was boosted by concurrent P. falciparum infections, and was associated with a lower risk of clinical episodes of malaria. Nine of the 14 vaccine candidates tested induced Ab-NK, including some less well-characterized antigens: P41, P113, MSP11, RHOPH3, and Pf_11363200. These data highlight an important role of Ab-NK activity in immunity against malaria and provide a potential mechanism for evaluating vaccine candidates.
Item Description:Gesehen am 29.03.2023
Physical Description:Online Resource
ISSN:1946-6242
DOI:10.1126/scitranslmed.abn5993

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