Journal
CELL
Volume 154, Issue 1, Pages 213-227Publisher
CELL PRESS
DOI: 10.1016/j.cell.2013.05.052
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Funding
- National Institute of Allergy and Infectious Diseases [HHSN272200800058C]
- American Lebanese Syrian Associated Charities (ALSAC)
- NIH/NIAID Center of Excellence for Influenza Research and Surveillance [HHSN266200700005C]
- NIGMS [U54 GM069338]
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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 antiinflammatory 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.
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