Document Type
Article
Department
Paediatrics and Child Health (East Africa)
Abstract
Memory-like natural killer (NK) cells with enhanced antibody-dependent cellular cytotoxicity (ADCC) have correlated with protection from uncomplicated malaria in prior studies. However, the role of NK cells in severe malaria (SM) has not been characterized. In Ugandan sites with moderate and low malaria transmission, we evaluated NK cell (CD56bright, CD56dim, CD56neg) phenotype and ADCC function by flow cytometry in children < 5 years of age with SM (n = 21) and control community children (CC, n = 19). Children with SM had similar total NK cell counts to CC. Children with SM had a higher proportion of LILRB1+ NK cells than CC. The level of malaria transmission in an area was related to NK cell function. In the low malaria transmission area only, children with SM had a higher proportion than CC of NK cells that degranulated, whereas children with SM from both low and moderate malaria transmission areas had lower IFN-γ production than CC. We next evaluated functional Boolean gating for degranulation and IFN-γ production (CD107a+/IFN-γ−, CD107a−/IFN-γ+, and CD107a+/IFN-γ+) in relation to memory-like and checkpoint/exhaustion NK cell markers in low and moderate malaria transmission SM and CC groups. We found there was a significant increase in degranulating only NK cells (CD107a+, IFN-γ−) in children with SM compared to CC solely in the low malaria transmission area. However, there was a significant decrease in NK cells that produced IFN-γ but did not degranulate (CD107a−, IFN-γ+) in children with SM compared to CC in both low and moderate transmission areas. Our data reveal compound functional differences in NK cells among children with SM living in areas of low versus moderate malaria transmission; however, a consistent finding is reduced NK cell IFN-γ production in SM, regardless of transmission intensity.
AKU Student
no
Publication (Name of Journal)
ImmunoHorizons
DOI
https://doi.org/10.1093/immhor/vlaf070
Recommended Citation
Turyasingura, G.,
Mellencamp, K. A.,
Namazzi, R.,
Opoka, R.,
John, C. C.,
Hart, G. T.
(2026). Altered natural killer cell function in children with severe malaria. ImmunoHorizons, 10(1), 1-13.
Available at:
https://ecommons.aku.edu/eastafrica_fhs_mc_paediatr_child_health/609
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.