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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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 |
Journal | Immunity
(Immunity)
Vol. 40
Issue 4
Pg. 554-68
(Apr 17 2014)
ISSN: 1097-4180 [Electronic] United States |
PMID | 24726877
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2014 Elsevier Inc. All rights reserved. |
Chemical References |
- Interferon Type I
- Receptors, Prostaglandin E, EP2 Subtype
- Receptors, Prostaglandin E, EP4 Subtype
- Intramolecular Oxidoreductases
- Prostaglandin-E Synthases
- Ptges protein, mouse
- Dinoprostone
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Topics |
- Animals
- Antigen Presentation
(drug effects)
- Apoptosis
(drug effects)
- Cells, Cultured
- Dinoprostone
(immunology, metabolism)
- Gene Expression Regulation
(drug effects)
- Immunity
(drug effects, genetics)
- Influenza A virus
(physiology)
- Interferon Type I
(genetics, metabolism)
- Intramolecular Oxidoreductases
(antagonists & inhibitors, genetics)
- Macrophages
(drug effects, immunology, virology)
- Mice
- Mice, Inbred C57BL
- Mice, Knockout
- Molecular Targeted Therapy
- Orthomyxoviridae Infections
(drug therapy, immunology)
- Prostaglandin-E Synthases
- Receptors, Prostaglandin E, EP2 Subtype
(antagonists & inhibitors)
- Receptors, Prostaglandin E, EP4 Subtype
(antagonists & inhibitors)
- T-Lymphocytes
(immunology, virology)
- Virus Replication
(genetics)
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