title: Metabolomics Investigation Reveals Metabolite Mediators Associated with Acute Lung Injury and Repair in a Murine Model of Influenza Pneumonia.
abstract: Influenza virus infection (IVI) can cause primary viral pneumonia, which may progress to acute lung injury (ALI) and respiratory failure with a potentially fatal outcome. At present, the interactions between host and influenza virus at molecular levels and the underlying mechanisms that give rise to IVI-induced ALI are poorly understood. We conducted a comprehensive mass spectrometry-based metabolic profiling of serum, lung tissue and bronchoalveolar lavage fluid (BALF) from a non-lethal mouse model with influenza A virus at 0, 6, 10, 14, 21 and 28 days post infection (dpi), representing the major stages of IVI. Distinct metabolite signatures were observed in mice sera, lung tissues and BALF, indicating the molecular differences between systematic and localized host responses to IVI. More than 100 differential metabolites were captured in mice sera, lung tissues and BALF, including purines, pyrimidines, acylcarnitines, fatty acids, amino acids, glucocorticoids, sphingolipids, phospholipids, etc. Many of these metabolites belonged to pulmonary surfactants, indicating IVI-induced aberrations of the pulmonary surfactant system might play an important role in the etiology of respiratory failure and repair. Our findings revealed dynamic host responses to IVI and various metabolic pathways linked to disease progression, and provided mechanistic insights into IVI-induced ALI and repair process.
authors.affiliation: Interdisciplinary Research Group in Infectious Diseases, Singapore-MIT Alliance for Research &Technology, Singapore.
authors.forename: Liang
authors.initials: L
authors.lastname: Cui
authors.affiliation: Interdisciplinary Research Group in Infectious Diseases, Singapore-MIT Alliance for Research &Technology, Singapore.
authors.forename: Dahai
authors.initials: D
authors.lastname: Zheng
authors.affiliation: Interdisciplinary Research Group in Infectious Diseases, Singapore-MIT Alliance for Research &Technology, Singapore.
authors.forename: Yie Hou
authors.initials: YH
authors.lastname: Lee
authors.affiliation: Interdisciplinary Research Group in Infectious Diseases, Singapore-MIT Alliance for Research &Technology, Singapore.|Department of Pharmacology, Yong Loo Lin School of Medicine, National University Health System, Singapore.
authors.forename: Tze Khee
authors.initials: TK
authors.lastname: Chan
authors.affiliation: Interdisciplinary Research Group in Infectious Diseases, Singapore-MIT Alliance for Research &Technology, Singapore.
authors.forename: Yadunanda
authors.initials: Y
authors.lastname: Kumar
authors.affiliation: Saw Swee Hock School of Public Health, National University of Singapore, Singapore.
authors.forename: Wanxing Eugene
authors.initials: WE
authors.lastname: Ho
authors.affiliation: Interdisciplinary Research Group in Infectious Diseases, Singapore-MIT Alliance for Research &Technology, Singapore.|Koch Institute for Integrative Cancer Research and Departments of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
authors.forename: Jian Zhu
authors.initials: JZ
authors.lastname: Chen
authors.affiliation: Interdisciplinary Research Group in Infectious Diseases, Singapore-MIT Alliance for Research &Technology, Singapore.|Departments of Biological Engineering and Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
authors.forename: Steven R
authors.initials: SR
authors.lastname: Tannenbaum
authors.affiliation: Interdisciplinary Research Group in Infectious Diseases, Singapore-MIT Alliance for Research &Technology, Singapore.|Saw Swee Hock School of Public Health, National University of Singapore, Singapore.|NUS Environment Research Institute, Singapore.
authors.forename: Choon Nam
authors.initials: CN
authors.lastname: Ong
mesh_terms: D055371:Acute Lung Injury / Q000473:pathology*; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D004195:Disease Models, Animal; D009980:Influenza A virus / Q000254:growth & development; D008168:Lung / Q000473:pathology; D013058:Mass Spectrometry; D055442:Metabolome; D055432:Metabolomics; D051379:Mice; D009976:Orthomyxoviridae Infections / Q000473:pathology*; D011024:Pneumonia, Viral / Q000473:pathology*; D044967:Serum / Q000737:chemistry; D013997:Time Factors