Interleukin-12 promotes gamma interferon-dependent neutrophil recruitment in the lung and improves protection against respiratory Streptococcus pneumoniae infection.
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.
Sun
Keer
K
Center for Immunology and Microbial Disease, MC-151, Albany Medical College, 47 New Scotland Avenue, Albany, NY 12208, USA.
Salmon
Sharon L
SL
Lotz
Steven A
SA
Metzger
Dennis W
DW
D000818:Animals; D007371:Interferon-gamma / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D018664:Interleukin-12 / Q000502:physiology*; D008168:Lung / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D020556:Neutrophil Infiltration / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology* / Q000382:microbiology / Q000473:pathology*; D011018:Pneumonia, Pneumococcal / Q000276:immunology / Q000378:metabolism* / Q000517:prevention & control; D013296:Streptococcus pneumoniae / Q000276:immunology*
D018664:Interleukin-12; D007371:Interferon-gamma