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Infection and Immunity, March 2007, p. 1196-1202, Vol. 75, No. 3
0019-9567/07/$08.00+0     doi:10.1128/IAI.01403-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Interleukin-12 Promotes Gamma Interferon-Dependent Neutrophil Recruitment in the Lung and Improves Protection against Respiratory Streptococcus pneumoniae Infection{triangledown}

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

Center for Immunology and Microbial Disease, Albany Medical College, Albany, New York 12208

Received 31 August 2006/ Returned for modification 25 October 2006/ Accepted 20 December 2006

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.

* Corresponding author. Mailing address: Center for Immunology and Microbial Disease, MC-151, Albany Medical College, 47 New Scotland Avenue, Albany, NY 12208. Phone: (518) 262-6750. Fax: (518) 262-6053. E-mail: Metzged{at}mail.amc.edu.

{triangledown} Published ahead of print on 8 January 2007.

Editor: J. N. Weiser

Infection and Immunity, March 2007, p. 1196-1202, Vol. 75, No. 3
0019-9567/07/$08.00+0     doi:10.1128/IAI.01403-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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