Autophagic protein ATG5 controls antiviral immunity via glycolytic reprogramming of dendritic cells against respiratory syncytial virus infection

Abstract

Respiratory syncytial virus (RSV) is a leading cause of respiratory tract infections in infants. Macroautophagy/autophagy is a catalytic metabolic process required for cellular homeostasis. Although intracellular metabolism is important for immune responses in dendritic cells, the link between autophagy and immunometabolism remains unknown. Here, we show that the autophagy-related protein ATG5 regulates immunometabolism.Atg5-deficient mouse dendritic cells showed increased CD8A(+)T-cell response and increased secretion of proinflammatory cytokines upon RSV infection. Transcriptome analysis showed thatAtg5deficiency alters the expression of metabolism-related genes.Atg5-deficient dendritic cells also showed increased activation of glycolysis and the AKT-MTOR-RPS6KB1 pathway and decreased mitochondrial activity, all of which are cellular signatures for metabolic activation. These cells also showed elevated CD8A(+)T-cell priming and surface major histocompatibility complex (MHC) class I expression. Our results suggested that ATG5 regulated host immune responses by modulating dendritic cell metabolism. These findings may help develop potential antiviral therapies that alter host immunity by regulating autophagy and immunometabolism.