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The role of interferon-gamma in murine pneumococcal pneumonia
Anita W Rijneveld1, Fanny N Lauw, Marc J Schultz
1Department of Experimental Internal Medicine, Tropical Medicine, and AIDS, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands. a.w.rijneveld@amc.uva.nl
Abstract:
To determine the role of interferon (IFN)-gamma in pneumonia, IFN-gamma receptor-deficient (IFN-gamma R(-/-)) and 129/Sv (wild-type [wt]) mice were inoculated intranasally with Streptococcus pneumoniae. Although mortality did not differ between the groups 48 h after inoculation, IFN-gamma R(-/-) mice had significantly fewer pneumococci in their lungs than the wt mice. Similarly, IFN-gamma(-/-) mice had fewer colony-forming units in lungs than wt mice. The relatively increased resistance of IFN-gamma R(-/-) mice was not related to favorable effects on defense mechanisms known to contribute to antibacterial immunity-that is, the neutrophilic influx was reduced and the cytokine and nitric oxide levels were similar or lower in IFN-gamma R(-/-) mice. In contrast, mice treated with anti-IFN-gamma did not demonstrate a consistently altered bacterial outgrowth, compared with mice treated with a control antibody. These data suggest that endogenous IFN-gamma, despite its protective role in defense against intracellular pathogens, does not serve a protective role during pneumococcal pneumonia.
Insights
Interferon-gamma (IFN-gamma) does not protect against pneumococcal pneumonia. Mice lacking the IFN-gamma receptor showed increased resistance to Streptococcus pneumoniae infection, suggesting a non-protective role for IFN-gamma in this context.
Area of Science:
- Immunology
- Microbiology
- Infectious Diseases
Background:
- Interferon-gamma (IFN-gamma) is crucial for defense against intracellular pathogens.
- Its role in bacterial pneumonia, specifically pneumococcal pneumonia, remains unclear.
Purpose of the Study:
- To investigate the role of endogenous IFN-gamma in host defense during Streptococcus pneumoniae pneumonia.
- To determine if IFN-gamma confers protection or exacerbates disease in a murine model.
Main Methods:
- Utilized IFN-gamma receptor-deficient (IFN-gamma R(-/-))) and IFN-gamma knockout (IFN-gamma(-/-))) mice, alongside wild-type (wt) controls.
- Inoculated mice intranasally with Streptococcus pneumoniae.
- Assessed bacterial load (colony-forming units), mortality, neutrophilic influx, and cytokine/nitric oxide levels.
Main Results:
- IFN-gamma R(-/-) and IFN-gamma(-/-) mice exhibited significantly fewer pneumococci in their lungs compared to wt mice.
- Mortality rates did not differ significantly between groups at 48 hours post-inoculation.
- Reduced neutrophilic influx and similar or lower cytokine/nitric oxide levels were observed in IFN-gamma R(-/-) mice, indicating no enhanced antibacterial immunity.
- Antibody-mediated neutralization of IFN-gamma did not consistently alter bacterial outgrowth.
Conclusions:
- Endogenous IFN-gamma does not play a protective role in pneumococcal pneumonia.
- The findings contrast with IFN-gamma's known protective function against intracellular pathogens.
- This suggests a complex, potentially non-beneficial role for IFN-gamma in certain bacterial infections.
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