Fungal vaccine-induced effector Tc17 cells need OXPHOS metabolism than glycolysis 2224

Abstract Description Immunocompromised patients are highly susceptible to invasive fungal infections with high case fatality rates. We have shown that experimental attenuated live fungal vaccine-induced Tc17 cells are stable without plasticity and long-lived, necessary to mediate sterilizing immunity during CD4+ T cell deficiency. We observed effector Tc17 cells were metabolically highly active with high rate of proliferation and protein biosynthesis. We hypothesized that effector Tc17 cells adopt high energy-yielding metabolic pathways to form stable long-lived memory cells. The studies suggest that T cell expansion involves a metabolic shift from OXPHOS to glycolysis. Using a mouse model of attenuated live fungal vaccination, we found that glucose was necessary for effector Tc17 cells with variable dependency during the phases of expansion. Contrary to established dogma, we found that the effector Tc17 cells preferentially channelled the glucose to OXPHOS than glycolysis, correlated with higher mitochondrial mass and membrane potential. Inhibition of OXPHOS shrunk the Tc17 responses while sparing Tc1 responses. Our RNAseq data authenticated the preferential use of OXPHOS by effector Tc17 cells, unlike Tc1 cells. Collectively, the effector Tc17 cells predominantly utilize glucose for energy through OXPHOS rather than glycolysis and the apt adjuvants should bolster OXPHOS-mediated Tc17 expansion to enhance killed/subunit fungal vaccine efficacy tailored for immunocompromised patients. Funding Sources Supported by NIH/NIAID R01A153522. Topic Categories Microbial, Parasitic, and Fungal Immunology (MPF)