Conference Abstract | Volume 8, Abstract NACNDC/19JASH018 (Oral) | Published:  05 Dec 2025

Characterization of NK cell phenotypes and function in children with symptomatic and asymptomatic plasmodium falciparum infection in a high transmission setting

Evelyn Nansubuga1, 2, &, Savannah Nicole Lewis3, Stephen Tukwasibwe2, Felistas Namirimu Nankya2, Patience Nayebare2, Yoweri Taremwa2, Annet Nalwoga2, Kenneth Musinguzi2, Martin Chamai2, Aloysius Ssemaganda2, Kattria van der Ploeg3, Kassie Press3, Kylie Camanag3, Jason Nideffer3, Isaac Ssewanyana2, Joaniter Nankabirwa2, 4, Moses Kamya2, 4, Emmanuel Arinaitwe2, Bernard Bagaya1, Prasanna Jagannathan3

1Department of Immunology and Molecular Biology, College of Health Sciences, Makerere, Kampala, Uganda, 2Infectious Diseases Research Collaboration Kampala Uganda, 3Department of Medicine Stanford University Stanford CA USA, 4School of Medicine, Makerere University Kampala Uganda

&Corresponding author: Evelyn Nansubuga, Department of Immunology and Molecular Biology, College of Health Sciences, Makerere, Kampala, Uganda, Email: evelynkiberu@gmail.com

Received: 11 Sep 2025, Accepted: 20 Oct 2025, Published: 05 Dec 2025

Domain: Infectious Disease Epidemiology

This is part of the Proceedings of the National Annual Communicable and Non-Communicable Diseases Conference (NACNDC) and 19th Joint Annual Scientific Health (JASH) Conference 2025

Keywords: Plasmodium falciparum, NK cells, asymptomatic malaria, symptomatic malaria, adaptive immunity

©Evelyn Nansubuga et al. Journal of Interventional Epidemiology and Public Health (ISSN: 2664-2824). This is an Open Access article distributed under the terms of the Creative Commons Attribution International 4.0 License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Cite this article: Evelyn Nansubuga et al., Characterization of NK cell phenotypes and function in children with symptomatic and asymptomatic plasmodium falciparum infection in a high transmission setting. Journal of Interventional Epidemiology and Public Health. 2025;8(ConfProc6):018. https://doi.org/10.37432/JIEPH-CONFPRO6-00018

Introduction

Malaria remains a leading cause of morbidity and mortality among children in sub-Saharan Africa, with Plasmodium falciparum infections manifesting either as asymptomatic or symptomatic disease.  Natural killer (NK) cells are increasingly recognized as important contributors to malaria immunity, yet their role in mediating protection in children remains poorly understood. 

Methods

This study aimed to characterize NK cell phenotypes and functions in children with symptomatic or asymptomatic malaria living in a transmission setting in Eastern Uganda. Peripheral blood mononuclear cell (PBMC) samples from 10 children enrolled in the MUSICAL study at symptomatic and asymptomatic timepoints; baseline, day 0 and day 14 were utilized for immunophenotyping and functional assays stimulated with IL-12, IL-15 and IL-18 and analysed using flow cytometry. NK cell subsets were defined as CD56bri, CD56dim and CD56neg, and further profiled for expression of adaptive markers (CD85j, CD57, NKG2C, LAG3, Siglec-7) and Killer-cell Immunoglobulin-like receptors (KIRs). Statistical comparisons were made using Wilcoxon signed rank test. 

Results

CD56 NK cells were the most abundant subset across infection states, while CD56neg NK cells expanded at infection and were enriched in asymptomatic cases. Adaptive markers such as CD85j were highly expressed on CD56neg, whereas NKG2C and CD57 predominated CD56dim NK cells. Cytokine profiling revealed that CD56bri NK cells were the main producers of IFN-y, TNF and IL-10, particularly in symptomatic infections on day 0. KIR expression was relatively stable but KIR2DL2/L3/S2 was enriched on CD56dim and CD56neg.

Conclusion

These findings suggest that repeated malaria exposure drives NK cell differentiation and expansion of adaptive-like CD56neg, which may contribute to clinical tolerance. The duo pro- and anti-inflammatory cytokine responses highlight NK cells as both regulators and effectors of malaria immunity. This study provides novel insights into inmate immune adaptation in malaria and identifies NK cell subsets and markers that could inform vaccine development and biomarker discovery.

 
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Keywords

  • Plasmodium falciparum
  • NK cells
  • Asymptomatic malaria
  • Symptomatic malaria
  • Adaptive immunity
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