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

Prostaglandins Other Lipid Mediat. 2012 May;98(1-2):23-30. doi: 10.1016/j.prostaglandins.2012.03.002. Epub 2012 Apr 2.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

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


  • Reactive Oxygen Species
  • Receptors, Prostaglandin E
  • Tumor Necrosis Factor-alpha
  • Interleukin-12