title: PFKFB3-Driven Macrophage Glycolytic Metabolism Is a Crucial Component of Innate Antiviral Defense.
abstract: Signaling by viral nucleic acids and subsequently by type I IFN is central to antiviral innate immunity. These signaling events are also likely to engage metabolic changes in immune and nonimmune cells to support antiviral defense. In this study, we show that cytosolic viral recognition, by way of secondary IFN signaling, leads to upregulation of glycolysis preferentially in macrophages. This metabolic switch involves induction of glycolytic activator 6-phosphofructose-2-kinase and fructose-2,6-bisphosphatase (PFKFB3). Using a genetic inactivation approach together with pharmacological perturbations in mouse cells, we show that PFKFB3-driven glycolysis selectively promotes the extrinsic antiviral capacity of macrophages, via metabolically supporting the engulfment and removal of virus-infected cells. Furthermore, the antiviral function of PFKFB3, as well as some contribution of its action from the hematopoietic compartment, was confirmed in a mouse model of respiratory syncytial virus infection. Therefore, different from the long-standing perception of glycolysis as a proviral pathway, our findings establish an antiviral, immunometabolic aspect of glycolysis that may have therapeutic implications.
authors: State Key Laboratory of Pharmaceutical Biotechnology and Ministry of Education Key Laboratory of Model Animals for Disease Study, Model Animal Research Center of Nanjing University, Nanjing 210061, China; and.
authors: Hui
authors: 0000-0003-1170-0224
authors: H
authors: Jiang
authors: School of Medicine, Nanjing University, Nanjing 210093, China.
authors: Hengfei
authors: 0000-0001-5305-3112
authors: H
authors: Shi
authors: State Key Laboratory of Pharmaceutical Biotechnology and Ministry of Education Key Laboratory of Model Animals for Disease Study, Model Animal Research Center of Nanjing University, Nanjing 210061, China; and.
authors: Man
authors: M
authors: Sun
authors: State Key Laboratory of Pharmaceutical Biotechnology and Ministry of Education Key Laboratory of Model Animals for Disease Study, Model Animal Research Center of Nanjing University, Nanjing 210061, China; and.
authors: Yafeng
authors: 0000-0001-9301-9736
authors: Y
authors: Wang
authors: State Key Laboratory of Pharmaceutical Biotechnology and Ministry of Education Key Laboratory of Model Animals for Disease Study, Model Animal Research Center of Nanjing University, Nanjing 210061, China; and.
authors: Qingzhou
authors: Q
authors: Meng
authors: State Key Laboratory of Pharmaceutical Biotechnology and Ministry of Education Key Laboratory of Model Animals for Disease Study, Model Animal Research Center of Nanjing University, Nanjing 210061, China; and.
authors: Panpan
authors: P
authors: Guo
authors: State Key Laboratory of Pharmaceutical Biotechnology and Ministry of Education Key Laboratory of Model Animals for Disease Study, Model Animal Research Center of Nanjing University, Nanjing 210061, China; and.
authors: Yanlan
authors: Y
authors: Cao
authors: State Key Laboratory of Pharmaceutical Biotechnology and Ministry of Education Key Laboratory of Model Animals for Disease Study, Model Animal Research Center of Nanjing University, Nanjing 210061, China; and.
authors: Jiong
authors: J
authors: Chen
authors: State Key Laboratory of Pharmaceutical Biotechnology and Ministry of Education Key Laboratory of Model Animals for Disease Study, Model Animal Research Center of Nanjing University, Nanjing 210061, China; and.
authors: Xiang
authors: X
authors: Gao
authors: State Key Laboratory of Pharmaceutical Biotechnology and Ministry of Education Key Laboratory of Model Animals for Disease Study, Model Animal Research Center of Nanjing University, Nanjing 210061, China; and School of Medicine, Nanjing University, Nanjing 210093, China liujianghuai@nju.edu.cn erguang@nju.edu.cn.
authors: Erguang
authors: 0000-0002-3065-1336
authors: E
authors: Li
authors: State Key Laboratory of Pharmaceutical Biotechnology and Ministry of Education Key Laboratory of Model Animals for Disease Study, Model Animal Research Center of Nanjing University, Nanjing 210061, China; and liujianghuai@nju.edu.cn erguang@nju.edu.cn.
authors: Jianghuai
authors: 0000-0002-2382-9140
authors: J
authors: Liu
mesh_terms: D000818:Animals; D006019:Glycolysis / Q000276:immunology; D007113:Immunity, Innate; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D025481:Phosphofructokinase-2 / Q000172:deficiency / Q000378:metabolism*; D018357:Respiratory Syncytial Virus Infections / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000821:virology*
chemical_list: C000595376:PFKFB3 protein, mouse; D025481:Phosphofructokinase-2