Autophagic protein ATG5 controls antiviral immunity via glycolytic reprogramming of dendritic cells against respiratory syncytial virus infection
Autophagic protein ATG5 controls antiviral immunity via glycolytic reprogramming of dendritic cells against respiratory syncytial virus infection
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DOI：
10.1080/15548627.2020.1812218
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发表时间：
2020-08-29
期刊：
影响因子：
13.3
通讯作者：
Lee, Heung Kyu
中科院分区：
文献类型：
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作者：
Oh, Dong Sun;Park, Jang Hyun;Lee, Heung Kyu
呼吸道合胞病毒（RSV）是婴儿呼吸道感染的主要原因。巨自噬/自噬是细胞稳态所需的催化代谢过程。虽然细胞内代谢对树突状细胞的免疫应答很重要，但自噬和免疫代谢之间的联系仍然未知。在此，我们发现自噬相关蛋白ATG 5调节免疫代谢，ATG 5缺陷小鼠树突状细胞在RSV感染后表现出增加的CD 8A（+）T细胞应答和增加的促炎细胞因子分泌。转录组分析表明，Atg 5缺陷改变了代谢相关基因的表达，Atg 5缺陷的树突状细胞还表现出糖酵解和AKT-MTOR-RPS 6 KB 1通路的激活增加以及线粒体活性降低，这些都是代谢活化的细胞特征。这些细胞还显示出升高的CD 8A（+）T细胞引发和表面主要组织相容性复合体（MHC）I类表达。我们的研究结果表明，ATG 5通过调节树突状细胞代谢来调节宿主免疫应答。这些发现可能有助于开发潜在的抗病毒疗法，通过调节自噬和免疫代谢来改变宿主免疫力。
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.