tetano
Editor, Senior Moderator
Viral Immunol. 2019 Apr 19. doi: 10.1089/vim.2019.0016. [Epub ahead of print]
[h=1]Targeting Peroxisome Proliferator-Activated Receptor-Gamma Decreases Host Mortality After Influenza Infection in Obese Mice.[/h] Huang S[SUP]1,[/SUP][SUP]2,[/SUP][SUP]3[/SUP], Jiang L[SUP]1,[/SUP][SUP]2,[/SUP][SUP]3[/SUP], Cheon IS[SUP]1,[/SUP][SUP]2,[/SUP][SUP]3[/SUP], Sun J[SUP]1,[/SUP][SUP]2,[/SUP][SUP]3[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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-γ agonist, 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-γ expression 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-γ expression. Furthermore, modalities targeting macrophage PPAR-γ expression and/or function may serve as promising therapeutics to treat severe influenza infection in obese patients.
[h=4]KEYWORDS:[/h] ; macrophage; obesity
PMID: 31009317 DOI: 10.1089/vim.2019.0016
[h=1]Targeting Peroxisome Proliferator-Activated Receptor-Gamma Decreases Host Mortality After Influenza Infection in Obese Mice.[/h] Huang S[SUP]1,[/SUP][SUP]2,[/SUP][SUP]3[/SUP], Jiang L[SUP]1,[/SUP][SUP]2,[/SUP][SUP]3[/SUP], Cheon IS[SUP]1,[/SUP][SUP]2,[/SUP][SUP]3[/SUP], Sun J[SUP]1,[/SUP][SUP]2,[/SUP][SUP]3[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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-γ agonist, 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-γ expression 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-γ expression. Furthermore, modalities targeting macrophage PPAR-γ expression and/or function may serve as promising therapeutics to treat severe influenza infection in obese patients.
[h=4]KEYWORDS:[/h] ; macrophage; obesity
PMID: 31009317 DOI: 10.1089/vim.2019.0016