title: E-prostanoid 2 receptor signaling suppresses lung innate immunity against Streptococcus pneumoniae.
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.
authors.affiliation: Divisions of Infectious Diseases, The University of Michigan, Ann Arbor, MI 48109-5680, United States. daronoff@umich.edu
authors.forename: David M
authors.initials: DM
authors.lastname: Aronoff
authors.forename: Ingrid L
authors.initials: IL
authors.lastname: Bergin
authors.forename: Casey
authors.initials: C
authors.lastname: Lewis
authors.forename: Deepti
authors.initials: D
authors.lastname: Goel
authors.forename: Edmund
authors.initials: E
authors.lastname: O'Brien
authors.forename: Marc
authors.initials: M
authors.lastname: Peters-Golden
authors.forename: Peter
authors.initials: P
authors.lastname: Mancuso
mesh_terms: D000818:Animals; D005260:Female; D007113:Immunity, Innate / Q000235:genetics / Q000276:immunology*; D018664:Interleukin-12 / Q000378:metabolism; D051379:Mice; D008817:Mice, Mutant Strains; D011008:Pneumococcal Infections / Q000276:immunology; D017382:Reactive Oxygen Species / Q000378:metabolism; D018078:Receptors, Prostaglandin E / Q000235:genetics / Q000378:metabolism*; D013296:Streptococcus pneumoniae / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D018078:Receptors, Prostaglandin E; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12