Interferon-γ production by neutrophils during bacterial pneumonia in mice

Mitsuhiro Yamada, John C. Gomez, Pauline E. Chugh, Clifford A. Lowell, Mary C. Dinauer, Dirk P. Dittmer, Claire M. Doerschuk

Research output: Contribution to journalArticlepeer-review

100 Scopus citations

Abstract

Rationale: Neutrophils are usually the first circulating leukocytes to respond during bacterial pneumonia. Their expression of oxidants, proteases, and other mediators present in granules is well documented, but their ability to produce mediators through transcription and translation after migration to an inflammatory site has been appreciated only more recently. Interferon (IFN)-γ is a cytokine with many functions important in host defense and immunity. Objectives: To examine the expression and function of IFN-γ in bacterial pneumonias. Methods: IFN-γ mRNA and protein were measured in digests of mouse lungs with 24-hour bacterial pneumonia. Bacterial clearance was studied with IFN-γ-deficient mice. Measurements and Main Results: Streptococcus pneumoniae and Staphylococcus aureus each induce expression of IFN-γ mRNA and protein by neutrophils by 24 hours. Only neutrophils that have migrated into pneumonic tissue produce IFN-γ. Deficiency of Hck/Fgr/Lyn, Rac2, or gp91phox prevents IFN-γ production. IFN-γ enhances bacterial clearance and is required for formation of neutrophil extracellular traps. In contrast, Pseudomonas aeruginosa and Escherichia coli induce production of IFN-γ mRNA but not protein. During pneumonia induced by E. coli but not S. pneumoniae, neutrophils produce microRNAs that target the 3′ untranslated region of the IFN-γ gene. Conclusions: S. pneumoniae and S. aureus, but not P. aeruginosa and E. coli, induce emigrated neutrophils to produce IFN-γ within 24 hours. Hck/Fgr/Lyn, Rac2, and NADPH oxidase are required for IFN-γ production. IFN-γ facilitates bacterial clearance at least in part through regulating formation of neutrophil extracellular traps. Differential expression by neutrophils of microRNAs that target the 3′ untranslated region of the IFN-γ gene may contribute to the pathogen-specific regulation of translation.

Original languageEnglish
Pages (from-to)1391-1401
Number of pages11
JournalAmerican journal of respiratory and critical care medicine
Volume183
Issue number10
DOIs
StatePublished - May 15 2011

Keywords

  • Host defense
  • Infection
  • Inflammation
  • Innate immunity

Fingerprint

Dive into the research topics of 'Interferon-γ production by neutrophils during bacterial pneumonia in mice'. Together they form a unique fingerprint.

Cite this