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 journalArticle

18 Citations (Scopus)

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

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Protein Deficiency
Fatty Acid-Binding Proteins
H1N1 Subtype Influenza A Virus
Orthomyxoviridae
Pneumonia
Influenza A virus
Human Influenza
Infection
Inflammation
Lung
Anti-Inflammatory Agents
Peroxisome Proliferator-Activated Receptors
Neutrophil Infiltration
Adaptive Immunity
Virus Diseases
Viral Load
Respiratory System
Lipid Peroxidation
Lung Diseases
Oxidative Stress

Keywords

  • FABP5
  • Inflammation
  • Influenza A
  • Lipid peroxidation

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

Cite this

FABP5 deficiency enhances susceptibility to H1N1 influenza a virus-induced lung inflammation. / Gally, Fabienne; Kosmider, Beata; Weaver, Michael R.; Pate, Kathryn M.; Hartshorn, Kevan L.; Oberley-Deegan, Rebecca E.

In: American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol. 305, No. 1, 01.07.2013, p. L64-L72.

Research output: Contribution to journalArticle

Gally, Fabienne ; Kosmider, Beata ; Weaver, Michael R. ; Pate, Kathryn M. ; Hartshorn, Kevan L. ; Oberley-Deegan, Rebecca E. / FABP5 deficiency enhances susceptibility to H1N1 influenza a virus-induced lung inflammation. In: American Journal of Physiology - Lung Cellular and Molecular Physiology. 2013 ; Vol. 305, No. 1. pp. L64-L72.
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