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Does Chlamydia trachomatis MoPn enter a microbiologically-inapparent state during experimental infection of the mouse
1Department of Microbial Infectivity, SmithKline Beecham Pharmaceuticals, Surrey, U.K.
Abstract:
Microbiologically-inapparent chlamydial infection may contribute towards the immunopathogenesis of these diseases. Although morphologically and physiologically aberrant non-cultivable chlamydiae can be induced reversibly in cell culture, evidence for these forms in infections of animals and humans is indirect. A mouse model of salpingitis caused by the mouse pneumonitis biovar of Chlamydia trachomatis (MoPn) was used to determine the existence of non-cultivable organisms in vivo. Following intravaginal inoculation, mice yielded high chlamydial counts for 7-14 dyas, with a decline in culture-positivity by 21-28 days. A significant elevation of IFN gamma production in infected tissues was measured for 21 days and, from 28-70 days, all mice were culture-negative and developed characteristic hydrosalpinges. MoPn was detected by PCR in vaginal swabs of 80% and 69% respectively of culture-negative animals at 21 and 28 days. In a second study, 100%, 63% and 50% of culture-negative genital tissue homogenates were PCR-positive at 21, 28 and 42 days. Immunosuppression with either cyclophosphamide or hydrocortisone failed to regenerate cultivable chlamydiae. Tissues were disrupted by homogenization and inoculated intranasally to MF1 mice which are extremely susceptible to MoPn, but all culture-negative specimens were non-infectious. The significance of the PCR-positive culture-negative specimens requires further investigation, since these may represent a non-cultivable state in the deeper tissues of the mouse genital tract which may be beyond the reach of reactivating triggers.
Insights
Non-cultivable Chlamydia trachomatis may persist in mice, detected by PCR even when cultures are negative. This suggests a dormant state in vivo, potentially impacting disease development and treatment strategies.
Area of Science:
- Microbiology
- Immunology
- Infectious Diseases
Background:
- Chlamydial infections can contribute to disease pathogenesis.
- Non-cultivable Chlamydia forms are known in vitro but their in vivo existence is unclear.
Purpose of the Study:
- To investigate the in vivo existence of non-cultivable Chlamydia trachomatis (MoPn) in a mouse model.
- To determine if immunosuppression can revive cultivable Chlamydia from non-infectious states.
Main Methods:
- A mouse model of salpingitis induced by MoPn.
- Chlamydial detection using culture and PCR in vaginal swabs and genital tissues.
- Assessment of IFN-gamma production.
- Immunosuppression with cyclophosphamide or hydrocortisone.
Main Results:
- Culture positivity declined over time, with mice becoming culture-negative by 28-70 days post-infection.
- PCR detected MoPn in culture-negative samples, indicating persistence.
- Immunosuppression did not restore cultivable Chlamydia.
- Culture-negative specimens were non-infectious in a secondary mouse model.
Conclusions:
- Non-cultivable Chlamydia may exist in vivo in mouse genital tracts.
- PCR-positive, culture-negative findings suggest a dormant or non-cultivable state.
- Further research is needed to understand the significance of these persistent forms.