Thursday, April 25, 2024
4/25/2024
Project Summary/Abstract Malaria is a significant global health problem in which we still fail to understand many protective features of the immune response. Natural killer (NK) cells produce inflammatory cytokines during the early stages of infection, yet have also been shown in viral models to limit T cell and B cell responses. We recently demonstrated that NK cell- produced IL-10 can limit CD8+ T cell activity during experimental cerebral malaria and thereby rescue mice from fatal, CD8+ T cell-mediated immunopathology. Using newly generated mouse strains, we will visual the location and cellular interactions of NK cells in the brain and establish the cellular targets of NK cell-derived IL-10 during cerebral disease. Our studies will also determine if distinct human NK cell subsets are more efficient at producing IL-10, and if these cells correlate with protection from malaria symptoms in humans. Finally, we will investigate the impact of NK cell-derived IL-10 on the development and function of memory CD8+ T cells. Our objective is to understand how NK cell regulatory functions like IL-10 production decrease immunopathology and symptomatic infection, and shape the developing T cell response. The proposed work will determine the consequences of NK cell-derived IL-10 during the immune response to malaria and reveal ways to exploit regulatory NK cell function, thereby improving immunity in populations at risk for severe disease.
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