Interleukin-12 promotes gamma interferon-dependent neutrophil recruitment in the lung and improves protection against respiratory Streptococcus pneumoniae infection

Keer Sun, Sharon L. Salmon, Steven A. Lotz, Dennis W. Metzger

Research output: Contribution to journalArticle

99 Scopus citations

Abstract

The ability of exogenous interleukin-12 (IL-12) to elicit protective innate immune responses against the extracellular pathogen Streptococcus pneumoniae was tested by infecting BALB/c mice intranasally (i.n.) with S. pneumoniae after i.n. administration of IL-12. It was found that administration of IL-12 resulted in lower bacterial burdens in the infected mice and significantly improved survival rates. All IL-12-treated mice contained higher levels of pulmonary gamma interferon (IFN-γ) after infection and significantly more neutrophils than infected mice not treated with IL-12. IFN-γ was found to be essential for IL-12-induced resistance and for neutrophil influx into the lungs, and the observed changes correlated with increased levels of the IL-8 homologue keratinocyte-derived chemokine (KC). In addition, in vitro tumor necrosis factor alpha (TNF-α) production by alveolar macrophages stimulated with heat-killed pneumococci was enhanced by IFN-γ, and TNF-α in turn could enhance production of KC by lung cells. Finally, IL-12-induced protection was dependent upon the presence of neutrophils and the KC receptor CXCR2. Taken together, the results indicate that exogenous IL-12 can improve innate defense in the lung against S. pneumoniae by inducing IFN-γ production, which in turn enhances chemokine expression, and promotes pulmonary neutrophil recruitment into the infected lung. The findings show that IL-12 and IFN-γ can mediate a protective effect against respiratory infection caused by extracellular bacterial pathogens.

Original languageEnglish (US)
Pages (from-to)1196-1202
Number of pages7
JournalInfection and immunity
Volume75
Issue number3
DOIs
Publication statusPublished - Mar 1 2007

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ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

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