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A role in vivo for tumor necrosis factor alpha in host defense against Chlamydia trachomatis
D M Williams1, D M Magee, L F Bonewald
1Infectious Diseases Section, Audie L. Murphy Memorial Veterans' Hospital, San Antonio, Texas.
Abstract:
In a mouse model of pneumonia caused by murine Chlamydia trachomatis (mouse pneumonitis agent [MoPn]), tumor necrosis factor alpha (TNF-alpha) antigen and bioactivity were demonstrated in vivo in the lung during MoPn infection in both athymic (nude) and heterozygous (nu/+) mice. Antibody to TNF-alpha that was exogenously given neutralized the TNF-alpha in the lung, significantly accelerated mortality, and caused a borderline increase in MoPn counts in the lung by culture in nu/+ mice. Lipopolysaccharide-induced TNF-alpha activity or injections of recombinant murine TNF-alpha significantly but modestly protected nu/+ mice against MoPn-induced mortality. TNF-alpha is produced in vivo during C. trachomatis infection and plays a role in host defense.
Insights
Tumor necrosis factor alpha (TNF-alpha) is produced during Chlamydia trachomatis pneumonia in mice. Neutralizing TNF-alpha accelerated mortality, while its administration offered modest protection, indicating its role in host defense.
Area of Science:
- Immunology
- Microbiology
- Infectious Diseases
Background:
- Chlamydia trachomatis (mouse pneumonitis agent [MoPn]) causes pneumonia in mice.
- Tumor necrosis factor alpha (TNF-alpha) is a key inflammatory cytokine.
- The role of TNF-alpha in Chlamydia-induced pneumonia requires further elucidation.
Purpose of the Study:
- To investigate the role of TNF-alpha in the host immune response to Chlamydia trachomatis (MoPn) pneumonia in a murine model.
- To determine the effects of TNF-alpha neutralization and administration on disease progression and mortality.
Main Methods:
- Induction of pneumonia in athymic (nude) and heterozygous (nu/+) mice using MoPn.
- Detection of TNF-alpha antigen and bioactivity in lung tissue.
- Administration of anti-TNF-alpha antibody or recombinant murine TNF-alpha.
- Assessment of mortality, lung MoPn counts, and TNF-alpha activity.
Main Results:
- TNF-alpha was detected in the lungs of infected mice.
- Neutralization of TNF-alpha accelerated mortality and increased MoPn counts in nu/+ mice.
- Administration of TNF-alpha or lipopolysaccharide-induced TNF-alpha activity provided modest protection against MoPn-induced mortality.
Conclusions:
- TNF-alpha is produced in vivo during Chlamydia trachomatis infection.
- TNF-alpha plays a significant role in host defense against Chlamydia-induced pneumonia.
- Targeting TNF-alpha may represent a therapeutic strategy for Chlamydia infections.