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Role of tumor necrosis factor alpha in pathogenesis of pneumococcal pneumonia in mice
K Takashima1, K Tateda, T Matsumoto
1Department of Microbiology, Toho University School of Medicine, Tokyo, Japan. takasima@lab.takeda.co.jp
Abstract:
The production and role of tumor necrosis factor alpha (TNF-alpha) in pneumococcal pneumonia were investigated in a mouse pneumonia model. When approximately 10(6) CFU of Streptococcus pneumoniae TUM19 were used to inoculate CBA/J mice intranasally, TNF-alpha levels in the lungs and serum began to increase from 1 and 3 days after infection, respectively, concomitantly with the increase in bacterial counts in the lungs. Anti-TNF-alpha antibody accelerated bacterial proliferation in the blood and the death of the mice. Although serum levels of immunoglobulin G antibody against the infecting bacteria were not affected by the anti-TNF-alpha antibody treatment, neutrophil counts in the blood were decreased by the treatment. These results suggest that TNF-alpha produced in the course of pneumococcal pneumonia prevents bacteremia by increasing the number of neutrophils in the blood.
Insights
Tumor necrosis factor alpha (TNF-alpha) increases during pneumococcal pneumonia. Blocking TNF-alpha worsens bacterial infection and mouse survival, suggesting its crucial role in fighting bacteremia.
Area of Science:
- Immunology
- Infectious Diseases
- Microbiology
Background:
- Pneumococcal pneumonia is a significant global health concern.
- The role of tumor necrosis factor alpha (TNF-alpha) in host defense during bacterial pneumonia requires further elucidation.
Purpose of the Study:
- To investigate the production and function of TNF-alpha in a mouse model of pneumococcal pneumonia.
- To determine the impact of TNF-alpha on bacterial load, host survival, and immune cell response.
Main Methods:
- Intranasal inoculation of CBA/J mice with Streptococcus pneumoniae.
- Measurement of TNF-alpha levels in lungs and serum post-infection.
- Administration of anti-TNF-alpha antibody to assess its effects on bacterial proliferation, survival, and immune cell counts.
Main Results:
- TNF-alpha levels increased in lungs and serum following S. pneumoniae infection, correlating with bacterial counts.
- Anti-TNF-alpha antibody treatment led to accelerated bacterial proliferation in the blood and increased mortality.
- Neutrophil counts in the blood were reduced in mice treated with anti-TNF-alpha antibody.
- Serum immunoglobulin G antibody levels against the bacteria were not significantly affected by anti-TNF-alpha antibody treatment.
Conclusions:
- TNF-alpha plays a critical protective role in pneumococcal pneumonia.
- The protective effect of TNF-alpha appears to be mediated, at least in part, by enhancing neutrophil recruitment to combat bacteremia.
- Targeting TNF-alpha may exacerbate pneumococcal infections, highlighting its importance in host defense.