Targeted Prostaglandin E2 Inhibition Enhances Antiviral Immunity through Induction of Type I Interferon and Apoptosis in Macrophages Academic Article uri icon

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abstract

  • Aspirin gained tremendous popularity during the 1918 Spanish Influenza virus pandemic, 50 years prior to the demonstration of their inhibitory action on prostaglandins. Here, we show that during influenza A virus (IAV) infection, prostaglandin E2 (PGE2) was upregulated, which led to the inhibition of type I interferon (IFN) production and apoptosis in macrophages, thereby causing an increase in virus replication. This inhibitory role of PGE2 was not limited to innate immunity, because both antigen presentation and T cell mediated immunity were also suppressed. Targeted PGE2 suppression via genetic ablation of microsomal prostaglandin E-synthase 1 (mPGES-1) or by the pharmacological inhibition of PGE2 receptors EP2 and EP4 substantially improved survival against lethal IAV infection whereas PGE2 administration reversed this phenotype. These data demonstrate that the mPGES-1-PGE2 pathway is targeted by IAV to evade host type I IFN-dependent antiviral immunity. We propose that specific inhibition of PGE2 signaling might serve as a treatment for IAV.

authors

  • Coulombe, François
  • Jaworska, Joanna
  • Verway, Mark
  • Tzelepis, Fanny
  • Massoud, Amir
  • Gillard, Joshua
  • Wong, Gary
  • Kobinger, Gary
  • Xing, Zhou
  • Couture, Christian
  • Joubert, Philippe
  • Fritz, Jörg H
  • Powell, William S
  • Divangahi, Maziar

publication date

  • April 2014

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