Title: E-prostanoid 2 receptor signaling suppresses lung innate immunity against Streptococcus pneumoniae.

Authors: Aronoff, David M; Bergin, Ingrid L; Lewis, Casey; Goel, Deepti; O'Brien, Edmund; Peters-Golden, Marc; Mancuso, Peter

Published In Prostaglandins Other Lipid Mediat, (2012 May)

Abstract: Pneumonia is a major global health problem. Prostaglandin (PG) E(2) is an immunomodulatory lipid with anti-inflammatory, immunosuppressive, and pro-resolving actions. Data suggest that the E-prostanoid (EP) 2 receptor mediates immunomodulatory effects of PGE(2), but the extent to which this occurs in Streptococcus pneumoniae infection is unknown. Intratracheal lung infection of C57BL/6 mice possessing (EP2(+/+)) or lacking (EP2(-/-)) the EP2 receptor was performed, as were in vitro studies of alveolar macrophage (AM) host defense functions. Bacterial clearance and survival were significantly improved in vivo in EP2(-/-) mice and it correlated with greater neutrophilic inflammation and higher lung IL-12 levels. Upon ex vivo challenge with pneumococcus, EP2(-/-)cells expressed greater amounts of TNF-α and MIP-2 than did EP2(+/+) AMs, and had improved phagocytosis, intracellular killing, and reactive oxygen intermediate generation. These data suggest that PGE(2)-EP2 signaling may provide a novel pharmacological target for treating pneumococcal pneumonia in combination with antimicrobials.

PubMed ID: 22575745

MeSH Terms: Animals; Female; Immunity, Innate/genetics; Immunity, Innate/immunology*; Interleukin-12/metabolism; Mice; Mice, Mutant Strains; Pneumococcal Infections/immunology; Reactive Oxygen Species/metabolism; Receptors, Prostaglandin E/genetics; Receptors, Prostaglandin E/metabolism*; Streptococcus pneumoniae/immunology*; Tumor Necrosis Factor-alpha/metabolism