NK cell cytotoxicity is transiently enhanced during acute malaria and modulated by the host microenvironment.
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Xi P, Sandoz PA, Lautenbach MJ, Bilev E, Önfelt B, Färnert A, Hammer Q, Sundling C
JCI Insight 11 (11) - [2026-06-08; online 2026-04-21]
Natural killer (NK) cells are pivotal in the early immune response to Plasmodium falciparum infection, yet their functional dynamics and regulation remain incompletely understood. In a longitudinal study of patients with malaria in a nonendemic setting, we observed a transient but potent activation of NK cell cytotoxicity during acute malaria, characterized by rapid granzyme B-mediated killing and elevated expression of genes associated with cytotoxicity (PRF1, GZMB, and GZMA). This heightened activity was supported by increased plasma levels of granzymes and proinflammatory cytokines, which enhanced NK cell function in vitro. However, plasma samples from clinical malaria also contained inhibitory mediators, including soluble cytokine receptors, which dampened NK cell responses. These findings reveal that the host microenvironment orchestrates a tightly regulated NK cell response that potentiates cytotoxicity during acute infection and rapidly downmodulates it after treatment. Understanding this balance between activation and suppression may inform strategies to harness NK cells for malaria control while minimizing immunopathology.
NGI Stockholm (Genomics Applications) [Service]
NGI Stockholm (Genomics Production) [Service]
National Genomics Infrastructure [Service]
PubMed 42013130
DOI 10.1172/jci.insight.198687
Crossref 10.1172/jci.insight.198687
pmc: PMC13313507
pii: 198687