RESUMEN
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.
Asunto(s)
Linfocitos T CD8-positivos/metabolismo , Reactividad Cruzada/inmunología , Células Endoteliales/metabolismo , Proteína Forkhead Box O1/metabolismo , Interleucina-6/metabolismo , Hígado/citología , Animales , Diferenciación Celular/genética , Respiración de la Célula , Células Endoteliales/citología , Células Endoteliales/ultraestructura , Glucólisis , Masculino , Metabolómica , Ratones Endogámicos C57BL , Mitocondrias/metabolismo , Fosforilación Oxidativa , Transducción de Señal , Receptor Toll-Like 4/metabolismo , Transcripción GenéticaRESUMEN
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.