Restoring glucose uptake rescues neutrophil dysfunction and protects against systemic fungal infection in mouse models of kidney disease
Chetan V. Jawale, Kritika Ramani, Dedong Li, Bianca M. Coleman, Rohan S. Oberoi, Saran Kupul, Li Lin, Jigar V. Desai, Greg M. Delgoffe, Michail S. Lionakis, Filitsa Bender, Alexander J. Prokopienko, Thomas D. Nolin, Sarah L. Gaffen, Partha S. Biswas
Abstract
in mice. Consequently, pharmacological inhibition of GSK3β restored glucose uptake and rescued ROS production and candidacidal function of neutrophils in uremic mice. Similarly, neutrophils isolated from patients with kidney disease and undergoing hemodialysis showed similar defect in the fungal killing activity, a phenotype rescued in the presence of a GSK3β inhibitor. These findings reveal a mechanism of neutrophil dysfunction during uremia and suggest a potentially translatable therapeutic avenue for treatment of disseminated candidiasis.