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In Vitro Assay of Plasmodium-Infected Red Blood Cell Killing by Cytotoxic Lymphocytes

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Altered natural killer cell function in children with severe malaria.

Grace Turyasingura¹, Kagan A Mellencamp², Ruth Namazzi³

¹Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN, United States.

|January 6, 2026

Summary

Severe malaria (SM) in children is linked to altered natural killer (NK) cell function, with reduced IFN-γ production consistently observed across different malaria transmission levels. NK cell degranulation varied by transmission intensity.

Keywords:

Plasmodium falciparum cerebral malaria natural killer cells severe malaria severe malarial anemia

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Published on: January 2, 2013

Area of Science:

Immunology
Infectious Diseases
Pediatrics

Background:

Memory-like natural killer (NK) cells enhance antibody-dependent cellular cytotoxicity (ADCC) and are linked to protection from uncomplicated malaria.
The role of NK cells in severe malaria (SM) remains poorly understood.

Purpose of the Study:

To characterize NK cell phenotype and function in children with severe malaria (SM) compared to healthy controls.
To investigate the impact of malaria transmission intensity on NK cell responses in SM.

Main Methods:

Flow cytometry was used to analyze NK cell subsets (CD56bright, CD56dim, CD56neg) and ADCC function.
Phenotypic analysis included LILRB1 expression and functional assays for degranulation (CD107a) and IFN-γ production.
Evaluated NK cell responses in children with SM and community controls (CC) from low and moderate malaria transmission areas in Uganda.

Main Results:

Children with SM had similar total NK cell counts but a higher proportion of LILRB1+ NK cells compared to CC.
NK cell degranulation was increased in SM children only in low transmission areas.
Children with SM exhibited reduced IFN-γ production from NK cells, irrespective of malaria transmission intensity.

Conclusions:

Severe malaria is associated with distinct NK cell functional profiles that differ based on malaria transmission intensity.
Reduced NK cell IFN-γ production is a consistent finding in children with severe malaria, regardless of transmission levels.
These findings highlight the complex role of NK cells in severe malaria pathogenesis.