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- Title
Anti-merozoite antibodies induce natural killer cell effector function and are associated with immunity against malaria.
- Authors
Odera, Dennis O.; Tuju, James; Mwai, Kennedy; Nkumama, Irene N.; Fürle, Kristin; Chege, Timothy; Kimathi, Rinter; Diehl, Stefan; Musasia, Fauzia K.; Rosenkranz, Micha; Njuguna, Patricia; Hamaluba, Mainga; Kapulu, Melissa C.; Frank, Roland; Osier, Faith H. A.; Abdi, Abdirahman I.; Chi, Primus Che; de Laurent, Zaydah; Jao, Irene; Kamuya, Dorcas
- Abstract
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. A different antibody angle: Natural killer (NK) cells have been shown to mediate immune responses against Plasmodium falciparum using multiple effector functions. Odera et al. now show that antibody-opsonized P. falciparum merozoites can induce NK cell degranulation and IFN-γ production. This response was not strain specific and reduced invasion of merozoites into uninfected red blood cells. Using a controlled human malaria infection study in adults, they observed that antibody-dependent NK (Ab-NK) cell activity correlated directly with the control of parasitemia. In addition, in a cohort of children living in an endemic malaria setting, Ab-NK frequency increased with age, was boosted during P. falciparum infection, and was linked to a reduced risk of clinical malaria. These findings highlight a key role for antibody-mediated NK cell responses during malaria. —CF
- Subjects
KILLER cells; IMMUNE response; CELL physiology; MALARIA; FC receptors; ERYTHROCYTES; IMMUNITY
- Publication
Science Translational Medicine, 2023, Vol 15, Issue 682, p1
- ISSN
1946-6234
- Publication type
Article
- DOI
10.1126/scitranslmed.abn5993