FABP5 deficiency enhances susceptibility to H1N1 influenza a virus-induced lung inflammation

Fabienne Gally, Beata Kosmider, Michael R. Weaver, Kathryn M. Pate, Kevan L. Hartshorn, Rebecca E. Oberley-Deegan

Research output: Contribution to journalArticlepeer-review

38 Scopus citations

Abstract

The early inflammatory response to influenza A virus infection contributes to severe lung disease and continues to pose a serious threat to human health. The mechanisms by which inflammatory cells invade the respiratory tract remain unclear. Uncontrolled inflammation and oxidative stress cause lung damage in response to influenza A infection. We have previously shown that the fatty acid binding protein 5 (FABP5) has anti-inflammatory properties. We speculate that, as a transporter of fatty acids, FABP5 plays an important protective role against oxidative damage to lipids during infection as well. Using FABP5-/- and wild-type (WT) mice infected with influenza A virus, we showed that FABP5-/- mice had increased cell infiltration of macrophages and neutrophils compared with WT mice. FABP5-/- mice presented lower viral burden but lost as much weight as WT mice. The adaptive immune response was also increased in FABP5-/- mice as illustrated by the accumulation of T and B cells in the lung tissues and increased levels of H1N1-specific IgG antibodies. FABP5 deficiency greatly enhanced oxidative damage and lipid peroxidation following influenza A infection and presented with sustained tissue inflammation. Interestingly, FABP5 expression decreased following influenza A infection in WT lung tissues that corresponded to a decrease in the anti-inflammatory molecule PPAR-γ activity. In conclusion, our results demonstrate a previously unknown contribution of FABP5 to influenza A virus pathogenesis by controlling excessive oxidative damage and inflammation. This property could be exploited for therapeutic purposes.

Original languageEnglish
Pages (from-to)L64-L72
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume305
Issue number1
DOIs
StatePublished - Jul 1 2013
Externally publishedYes

Keywords

  • FABP5
  • Inflammation
  • Influenza A
  • Lipid peroxidation

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