NK cell cytotoxicity is transiently enhanced during acute malaria and modulated by the host microenvironment
Year: 2026
Type: article
Study design: Observational Study
Abstract: 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.
Source: JCI Insight
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $4,100
Awards: G1725882849, G2027075982, G2249452043, G2703043632, G3029450460, G3032923332, Understanding acquisition and maintenance of immunity to malaria, G4408466800, Acquired immunity to malaria: addressing parasite diversity and immune maintenance, Decoding viral evolution in real time and assessing its impact on host innate immune responses, G5173161835, G5201961806, Immunomodulation and tolerance as a consequence of repeated or chronic infection, Understanding acquisition and maintenance of immunity to malaria, G6560050331, G6588298923, Immunity to malaria: importance of parasite diversity and host memory, G6647109171, G712881263, G8986025646
OpenAlex ID: W7155040574