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Infect Immun. 2007 Mar;75(3):1196-202. Epub 2007 Jan 8.

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

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1
Center for Immunology and Microbial Disease, MC-151, Albany Medical College, 47 New Scotland Avenue, Albany, NY 12208, USA.

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.

PMID:
17210665
PMCID:
PMC1828591
DOI:
10.1128/IAI.01403-06
[Indexed for MEDLINE]
Free PMC Article
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