title: Suppression of IRG-1 Reduces Inflammatory Cell Infiltration and Lung Injury in Respiratory Syncytial Virus Infection by Reducing Production of Reactive Oxygen Species.
abstract: Respiratory syncytial virus (RSV) infection is a common cause of lower respiratory tract illness in infants and children. RSV is a negative-sense, single-strand RNA (ssRNA) virus that mainly infects airway epithelial cells. Accumulating evidence indicates that reactive oxygen species (ROS) production is a major factor for pulmonary inflammation and tissue damage of RSV disease. We investigated immune-responsive gene-1 (IRG1) expression during RSV infection, since IRG1 has been shown to mediate innate immune response to intracellular bacterial pathogens by modulating ROS and itaconic acid production. We found that RSV infection induced IRG1 expression in human A549 cells and in the lung tissues of RSV-infected mice. RSV infection or IRG1 overexpression promoted ROS production. Accordingly, knockdown of IRG1 induction blocked RSV-induced ROS production and proinflammatory cytokine gene expression. Finally, we showed that suppression of IRG1 induction reduced immune cell infiltration and prevented lung injury in RSV-infected mice. These results therefore link IRG1 induction to ROS production and immune lung injury after RSV infection.
  
  
  
  RSV infection is among the most common causes of childhood diseases. Recent studies identify ROS production as a factor contributing to RSV disease. We investigated the cause of ROS production and identified IRG1 as a critical factor linking ROS production to immune lung injury after RSV infection. We found that IRG1 was induced in A549 alveolar epithelial cells and in mouse lungs after RSV infection. Importantly, suppression of IRG1 induction reduced inflammatory cell infiltration and lung injury in mice. This study links IRG1 induction to oxidative damage and RSV disease. It also uncovers a potential therapeutic target in reducing RSV-caused lung injury.
authors.affiliation: Medical School and State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Ren
authors.affiliation: Medical School and State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, China.|College of Life Sciences, Nanjing University, Nanjing, China.
authors.forename: Yuanzi
authors.initials: Y
authors.lastname: Lv
authors.affiliation: Nanjing Children's Hospital, Nanjing Medical University, Nanjing, China.
authors.forename: Yujie
authors.initials: Y
authors.lastname: Zhuo
authors.affiliation: Medical School and State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, China.|College of Life Sciences, Nanjing University, Nanjing, China.
authors.forename: Changmai
authors.initials: C
authors.lastname: Chen
authors.affiliation: Medical School and State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, China.
authors.forename: Hengfei
authors.initials: H
authors.lastname: Shi
authors.affiliation: Medical School and State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Guo
authors.affiliation: Nanjing Children's Hospital, Nanjing Medical University, Nanjing, China.
authors.forename: Guang
authors.initials: G
authors.lastname: Yang
authors.affiliation: Medical School and State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, China.
authors.forename: Yayi
authors.initials: Y
authors.lastname: Hou
authors.affiliation: Medical School and State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, China rxtan@nju.edu.cn erguang@nju.edu.cn.|College of Life Sciences, Nanjing University, Nanjing, China.
authors.forename: Ren Xiang
authors.initials: RX
authors.lastname: Tan
authors.affiliation: Medical School and State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, China rxtan@nju.edu.cn erguang@nju.edu.cn.|College of Life Sciences, Nanjing University, Nanjing, China.
authors.forename: Erguang
authors.identifier: http://orcid.org/0000-0002-3065-1336
authors.initials: E
authors.lastname: Li
mesh_terms: D000818:Animals; D002262:Carboxy-Lyases; D002460:Cell Line; D054884:Host-Pathogen Interactions; D006801:Humans; D006836:Hydro-Lyases / Q000378:metabolism*; D055370:Lung Injury / Q000473:pathology*; D051379:Mice; D011506:Proteins / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D018357:Respiratory Syncytial Virus Infections / Q000473:pathology*; D012136:Respiratory Syncytial Viruses / Q000472:pathogenicity*
chemical_list: D011506:Proteins; D017382:Reactive Oxygen Species; C561544:ACOD1 protein, human; D002262:Carboxy-Lyases; D006836:Hydro-Lyases; C487648:Acod1 protein, mouse