title: Lipidomic profiling of influenza infection identifies mediators that induce and resolve inflammation.
abstract: Bioactive lipid mediators play a crucial role in the induction and resolution of inflammation. To elucidate their involvement during influenza infection, liquid chromatography/mass spectrometry lipidomic profiling of 141 lipid species was performed on a mouse influenza model using two viruses of significantly different pathogenicity. Infection by the low-pathogenicity strain X31/H3N2 induced a proinflammatory response followed by a distinct anti-inflammatory response; infection by the high-pathogenicity strain PR8/H1N1 resulted in overlapping pro- and anti-inflammatory states. Integration of the large-scale lipid measurements with targeted gene expression data demonstrated that 5-lipoxygenase metabolites correlated with the pathogenic phase of the infection, whereas 12/15-lipoxygenase metabolites were associated with the resolution phase. Hydroxylated linoleic acid, specifically the ratio of 13- to 9-hydroxyoctadecadienoic acid, was identified as a potential biomarker for immune status during an active infection. Importantly, some of the findings from the animal model were recapitulated in studies of human nasopharyngeal lavages obtained during the 2009-2011 influenza seasons.
authors.affiliation: Seattle Biomedical Research Institute, Seattle, WA 98109, USA.
authors.forename: Vincent C
authors.initials: VC
authors.lastname: Tam
authors.forename: Oswald
authors.initials: O
authors.lastname: Quehenberger
authors.forename: Christine M
authors.initials: CM
authors.lastname: Oshansky
authors.forename: Rosa
authors.initials: R
authors.lastname: Suen
authors.forename: Aaron M
authors.initials: AM
authors.lastname: Armando
authors.forename: Piper M
authors.initials: PM
authors.lastname: Treuting
authors.forename: Paul G
authors.initials: PG
authors.lastname: Thomas
authors.forename: Edward A
authors.initials: EA
authors.lastname: Dennis
authors.forename: Alan
authors.initials: A
authors.lastname: Aderem
mesh_terms: D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism; D016207:Cytokines / Q000276:immunology; D004195:Disease Models, Animal; D015777:Eicosanoids / Q000276:immunology / Q000302:isolation & purification*; D005231:Fatty Acids, Unsaturated / Q000276:immunology / Q000302:isolation & purification*; D006801:Humans; D018836:Inflammation Mediators / Q000032:analysis; D053118:Influenza A Virus, H1N1 Subtype / Q000502:physiology*; D053122:Influenza A Virus, H3N2 Subtype / Q000502:physiology*; D007251:Influenza, Human / Q000276:immunology*; D008055:Lipids / Q000032:analysis*; D053858:Metabolic Networks and Pathways; D051379:Mice; D017817:Nasal Lavage Fluid / Q000276:immunology; D009976:Orthomyxoviridae Infections / Q000276:immunology*; D059467:Transcriptome
chemical_list: D016207:Cytokines; D015777:Eicosanoids; D005231:Fatty Acids, Unsaturated; D018836:Inflammation Mediators; D008055:Lipids; C495366:hydroxyoctadecadienoic acid; D001094:Arachidonate 5-Lipoxygenase