Title |
Targeted Prostaglandin E2 Inhibition Enhances Antiviral Immunity through Induction of Type I Interferon and Apoptosis in Macrophages
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Published in |
Immunity, April 2014
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DOI | 10.1016/j.immuni.2014.02.013 |
Pubmed ID | |
Authors |
François Coulombe, Joanna Jaworska, Mark Verway, Fanny Tzelepis, Amir Massoud, Joshua Gillard, Gary Wong, Gary Kobinger, Zhou Xing, Christian Couture, Philippe Joubert, Jörg H. Fritz, William S. Powell, Maziar Divangahi |
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. |
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Mendeley readers
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Student > Doctoral Student | 13 | 7% |
Student > Master | 13 | 7% |
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