RESUMO
Liver sinusoidal endothelial cells (LSECs) are liver-resident antigen (cross)-presenting cells that generate memory CD8 T cells, but metabolic properties of LSECs and LSEC-primed CD8 T cells remain understudied. Here, we report that high-level mitochondrial respiration and constitutive low-level glycolysis support LSEC scavenger and sentinel functions. LSECs fail to increase glycolysis and co-stimulation after TLR4 activation, indicating absence of metabolic and functional maturation compared with immunogenic dendritic cells. LSEC-primed CD8 T cells show a transient burst of oxidative phosphorylation and glycolysis. Mechanistically, co-stimulatory IL-6 signaling ensures high FOXO1 expression in LSEC-primed CD8 T cells, curtails metabolic activity associated with T cell activation, and is indispensable for T cell functionality after re-activation. Thus, distinct immunometabolic features characterize non-immunogenic LSECs compared with immunogenic dendritic cells and LSEC-primed CD8 T cells with memory features compared with effector CD8 T cells. This reveals local features of metabolism and function of T cells in the liver.
Assuntos
Linfócitos T CD8-Positivos/metabolismo , Apresentação Cruzada/imunologia , Células Endoteliais/metabolismo , Proteína Forkhead Box O1/metabolismo , Interleucina-6/metabolismo , Fígado/citologia , Animais , Diferenciação Celular/genética , Respiração Celular , Células Endoteliais/citologia , Células Endoteliais/ultraestrutura , Glicólise , Masculino , Metabolômica , Camundongos Endogâmicos C57BL , Mitocôndrias/metabolismo , Fosforilação Oxidativa , Transdução de Sinais , Receptor 4 Toll-Like/metabolismo , Transcrição GênicaRESUMO
Protamine hydrochloride adsorbed onto citrated superparamagnetic iron oxide nanoparticles represents an efficient tool for capturing and concentration of hepatitis-C virus from plasma samples, improving the sensitivity of downstream analysis by nucleic acid testing.
