Journal Article

Prostaglandin E2 Induction during Mouse Adenovirus Type 1 Respiratory Infection Regulates Inflammatory Mediator Generation but Does Not Affect Viral Pathogenesis

McDonnell, Peter J., Mancuso, Peter, McCarthy, Mary K., Procario, Megan C., Aronoff, David M., Weinberg, Jason B., Crofford, Leslie J., Zhu, Lingqiao, Levine, Rachael E.

2013

Overview

Respiratory viruses cause substantial disease and are a significant healthcare burden. Virus-induced inflammation can be detrimental to the host, causing symptoms during acute infection and leading to damage that contributes to long-term residual lung disease. Prostaglandin E2 (PGE2) is a lipid mediator that is increased in response to many viral infections, and inhibition of PGE2 production during respiratory viral infection often leads to a decreased inflammatory response. We tested the hypothesis that PGE2 promotes inflammatory responses to mouse adenovirus type 1 (MAV-1) respiratory infection. Acute MAV-1 infection increased COX-2 expression and PGE2 production in wild type mice. Deficiency of the E prostanoid 2 receptor had no apparent effect on MAV-1 pathogenesis. Virus-induced induction of PGE2, IFN-γ, CXCL1, and CCL5 was reduced in mice deficient in microsomal PGE synthase-1 (mPGES-1(-/-) mice). However, there were no differences between mPGES-1(+/+) and mPGES-1(-/-) mice in viral replication, recruitment of leukocytes to airways or lung inflammation. Infection of both mPGES‑1(+/+) and mPGES-1(-/-) mice led to protection against reinfection. Thus, while PGE2 promotes the expression of a variety of cytokines in response to acute MAV-1 infection, PGE2 synthesis does not appear to be essential for generating pulmonary immunity.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Adenoviridae - immunology / Adenoviridae - pathogenicity / Adenoviruses / Animals / Chemokine CCL5 - genetics / Chemokine CCL5 - metabolism / Chemokine CXCL1 - genetics / Chemokine CXCL1 - metabolism / Cyclooxygenase-2 / Cytokines / Dinoprostone - genetics / Dinoprostone - metabolism / Enzymes / Fibroblasts / Health care / Hypotheses / Immunity / Immunology / Infections / Inflammation / Inflammatory response / Influenza / Interferon / Interferon-gamma - genetics / Interferon-gamma - metabolism / Internal medicine / Leukocyte migration / Leukocytes / Lung diseases / Male / Mice / Mice, Mutant Strains / Pathogenesis / Pediatrics / Production increases / Prostaglandin E2 / Prostaglandin-E synthase / Real-Time Polymerase Chain Reaction / Recruitment / Respiratory syncytial virus / Respiratory tract infection / Respiratory Tract Infections - immunology / Respiratory Tract Infections - metabolism / Respiratory Tract Infections - virology / Rodents / Streptococcus infections / Studies / Tuberculosis / Viral infections / Virus Replication - genetics / Virus Replication - physiology / Viruses / White blood cells / γ-Interferon