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Murine model of ocular infection by a human biovar of Chlamydia trachomatis
J A Whittum-Hudson1, T P O'Brien, R A Prendergast
1Wilmer Ophthalmological Institute, Johns Hopkins University, Baltimore, Maryland, USA.
Purpose:
A human biovar of Chlamydia trachomatis was used to develop a murine model of ocular chlamydial infection. The inbred mouse model will allow detailed immunologic studies during ocular infection, and use of a human biovar for infection may aid in identification of appropriate vaccine strategies against chlamydial infections.
Methods:
BALB/c, C3H/HeN, and C57B1/6J mice (n = 5 to 10 mice/group) were topically infected in the conjunctiva with C serovar of C. trachomatis. The effects were tested of single and repeated infection with 5000 inclusion-forming units (IFU) in 5 microliters and different inoculum doses. Conjunctival surfaces of both eyes were swabbed for microbiologic signs (isolation culture or direct fluorescent antibody staining) of infection over 4 to 6 weeks. Conjunctivae were removed for histopathologic study, and lymphocytes from draining cervical lymph nodes and spleens were tested for chlamydia-specific proliferative responses. Serum was obtained from all mice and tested for anti-chlamydial antibodies.
Results:
BALB/c and C3H/HeN mice developed dose-dependent microbiologic, histopathologic, and immunologic evidence of ocular infection. Eyes of mice were culture-positive from day 7 through at least day 21, with the peak of infection at days 10 to 14 after infection. Histopathologically, the development of conjunctival subepithelial mononuclear infiltration, exudate, and loss of goblet cells occurred within 1 week. Dose-dependent lymphoproliferative responses to whole chlamydial elementary bodies were observed; anti-chlamydial antibody was detected by immunoblotting only in infected mice.
Conclusions:
Several strains of inbred mice are susceptible to human chlamydial biovars and may provide a useful alternative disease model in which to study the immunopathogenesis of ocular chlamydial infection and test of vaccine candidates derived from clinically relevant human biovars.
Insights
A new mouse model using human Chlamydia trachomatis successfully mimics ocular infection, showing immune responses and potential for vaccine development against chlamydial eye disease.
Area of Science:
- Ophthalmology
- Infectious Diseases
- Immunology
- Microbiology
Background:
- Ocular chlamydial infections pose a significant global health challenge.
- Existing animal models may not fully recapitulate human disease or vaccine responses.
- Development of a relevant murine model is crucial for studying immunopathogenesis and testing interventions.
Purpose of the Study:
- To establish a murine model of ocular chlamydial infection using a human biovar of Chlamydia trachomatis.
- To enable detailed immunologic studies of ocular infection.
- To facilitate the identification of effective vaccine strategies against chlamydial infections.
Main Methods:
- Inbred mice (BALB/c, C3H/HeN, C57B1/6J) were topically infected with C. trachomatis (C serovar).
- Infection dynamics were assessed via microbiologic (culture, DFA), histopathologic, and immunologic (lymphocyte proliferation, antibody) analyses.
- Dose-dependency and effects of single vs. repeated infections were evaluated over 4-6 weeks.
Main Results:
- BALB/c and C3H/HeN mice exhibited dose-dependent ocular infection with microbiologic, histopathologic, and immunologic evidence.
- Culture positivity persisted from day 7 to at least day 21, peaking at days 10-14.
- Histopathology revealed conjunctival inflammation, exudate, and goblet cell loss; dose-dependent lymphoproliferative responses and anti-chlamydial antibodies were detected.
Conclusions:
- Inbred mice are susceptible to human chlamydial biovars, providing a viable model for ocular infection.
- This model allows for studying immunopathogenesis of ocular chlamydial infections.
- It serves as a valuable platform for testing vaccine candidates against clinically relevant human biovars.