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Role of endogenous gamma interferon in host defense against Chlamydia trachomatis infections
G M Zhong1, E M Peterson, C W Czarniecki
1Department of Pathology, University of California Irvine 92717.
Abstract:
BALB/c mice (6 to 8 weeks old) infected with Chlamydia trachomatis serovar L1 were sacrificed, and the yield of Chlamydia inclusion-forming units from the liver and lungs was measured in HeLa 229 cells. The yield of inclusion-forming units reached a peak at 3 days postinfection and then progressively declined. The mice infected with C. trachomatis had no detectable levels of gamma interferon (IFN-gamma) in their sera. However, stimulation of their spleen cells with either concanavalin A or heat-killed C. trachomatis resulted in the release of high levels of IFN-gamma (600 to 900 IU/ml) at 5 to 8 days postinfection. The increased release of IFN-gamma from the spleen cells paralleled the clearance of chlamydia from the liver and lungs. Sera and spleen cells from animals immunized with live C. trachomatis were transferred to recipient mice that were subsequently challenged with C. trachomatis. Transfer of spleen cells resulted in a reduction of the infection in the recipient animal as measured by the yield of chlamydia from the spleen, but transfer of the sera did not confer protective immunity. In addition, mice infected with C. trachomatis serovar L1 were treated with a hamster neutralizing monoclonal antibody to recombinant murine IFN-gamma (MAb-MuIFN-gamma). In the animals receiving the MAb-MuIFN-gamma, the yield of chlamydia from the lungs, spleen, and liver was significantly higher than from the control groups of mice. Histopathological analysis of tissues from the chlamydia-infected mice showed that the animals treated with the MAb-MuIFN-gamma had a significantly more extensive inflammatory reaction in their lungs, liver, and spleen.
Insights
Gamma interferon (IFN-gamma) plays a crucial role in controlling Chlamydia trachomatis infection in mice. Blocking IFN-gamma exacerbates chlamydial load and inflammation, highlighting its protective function.
Area of Science:
- Immunology
- Microbiology
- Infectious Diseases
Background:
- Chlamydia trachomatis is a significant human pathogen.
- The immune response to Chlamydia infection is complex and not fully understood.
- Gamma interferon (IFN-gamma) is a key cytokine involved in cell-mediated immunity.
Purpose of the Study:
- To investigate the role of IFN-gamma in the host immune response to Chlamydia trachomatis serovar L1 infection in BALB/c mice.
- To determine if IFN-gamma is essential for the clearance of Chlamydia from infected tissues.
- To assess the protective effects of spleen cell transfer and the impact of IFN-gamma neutralization on Chlamydia infection.
Main Methods:
- BALB/c mice were infected with Chlamydia trachomatis serovar L1.
- Chlamydia yield was measured in liver and lungs using inclusion-forming units in HeLa 229 cells.
- Spleen cells and sera from immunized mice were transferred to recipient mice.
- Mice were treated with a neutralizing monoclonal antibody to murine IFN-gamma (MAb-MuIFN-gamma).
- Histopathological analysis was performed on infected tissues.
Main Results:
- Chlamydia yield peaked at 3 days post-infection and then declined.
- Infected mice showed no detectable serum IFN-gamma, but spleen cells produced high levels upon stimulation.
- IFN-gamma production correlated with Chlamydia clearance from liver and lungs.
- Transfer of immune spleen cells reduced infection, but serum transfer did not confer protection.
- Neutralization of IFN-gamma significantly increased Chlamydia yield in lungs, spleen, and liver.
- MAb-MuIFN-gamma treatment led to more extensive inflammation in infected tissues.
Conclusions:
- IFN-gamma is critical for controlling Chlamydia trachomatis infection in mice.
- The immune response involving IFN-gamma contributes to the clearance of Chlamydia from host tissues.
- Targeting IFN-gamma may exacerbate Chlamydia pathogenesis and inflammation.