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

Infect Immun. 2007 Mar;75(3):1196-202. doi: 10.1128/IAI.01403-06. Epub 2007 Jan 8.

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-gamma) after infection and significantly more neutrophils than infected mice not treated with IL-12. IFN-gamma 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-alpha) production by alveolar macrophages stimulated with heat-killed pneumococci was enhanced by IFN-gamma, and TNF-alpha 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-gamma production, which in turn enhances chemokine expression, and promotes pulmonary neutrophil recruitment into the infected lung. The findings show that IL-12 and IFN-gamma can mediate a protective effect against respiratory infection caused by extracellular bacterial pathogens.

Publication types

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

MeSH terms

  • Animals
  • Interferon-gamma / deficiency
  • Interferon-gamma / genetics
  • Interferon-gamma / physiology*
  • Interleukin-12 / physiology*
  • Lung / immunology
  • Lung / metabolism*
  • Lung / microbiology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Neutrophil Infiltration / immunology*
  • Neutrophils / immunology*
  • Neutrophils / microbiology
  • Neutrophils / pathology*
  • Pneumonia, Pneumococcal / immunology
  • Pneumonia, Pneumococcal / metabolism*
  • Pneumonia, Pneumococcal / prevention & control
  • Streptococcus pneumoniae / immunology*

Substances

  • Interleukin-12
  • Interferon-gamma