Targeting Peroxisome Proliferator-Activated Receptor-Gamma Decreases Host Mortality After Influenza Infection in Obese Mice

Su Huang, Li Jiang, In Su Cheon, Jie Sun

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Obesity is an independent risk factor for severe influenza infection. However, the underlying cellular and molecular mechanisms are still incompletely understood. In this study, we have utilized a murine influenza infection model in genetic-induced obese (db/db) mice to explore the mechanisms by which obesity increases host susceptibility to influenza infection. We find that db/db mice have enhanced viral replication, exaggerated inflammatory responses, and dysregulated lung repair process after influenza infection, and consequently increased host mortality. Furthermore, we demonstrate that the transcription factor peroxisome proliferator-activated receptor-gamma (PPAR-γ), an important inflammation regulator, was downregulated in the lung macrophages of db/db mice after influenza infection. Strikingly, the treatment of 15-deoxy-Δ12, 14-prostaglandin J2 (15d-PGJ2), a PPAR-γagonist, largely rescued the survival of db/db mice after influenza infection. Interestingly, macrophage PPAR-γ-deficient mice exhibited enhanced mortality after influenza infection and 15d-PGJ2 fails to rescue host mortality in macrophage PPAR-γ-deficient mice, suggesting that PPAR-γexpression in macrophages is critical for the action of 15d-PGJ2. These data indicate that obesity attenuates lung antiviral immunity and hampers host recovery through the modulation of macrophage PPAR-γexpression. Furthermore, modalities targeting macrophage PPAR-γexpression and/or function may serve as promising therapeutics to treat severe influenza infection in obese patients.

Original languageEnglish (US)
Pages (from-to)161-169
Number of pages9
JournalViral Immunology
Volume32
Issue number4
DOIs
StatePublished - May 2019

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Keywords

  • PPAR-γ
  • macrophage
  • obesity

ASJC Scopus subject areas

  • Immunology
  • Molecular Medicine
  • Virology

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