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Published on: August 11, 2012
Infection of Hysterectomized Mice with Chlamydia muridarum and Chlamydia trachomatis
Chunfu Yang1, William M Whitmire1, Gail L Sturdevant2
1Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Abstract:
We studied infection and immunity of hysterectomized mice infected with Chlamydia muridarum and Chlamydia trachomatis to determine if there were differences between these species in their ability to infect vaginal squamous epithelial cells in vivo independently of proximal upper genital tract tissues. We found that C. muridarum readily colonized and infected vaginal squamous epithelial cells, whereas C. trachomatis did not. Primary infection of the vaginal epithelium with C. muridarum produced infections of a duration longer than that reported for normal mice. Infection resulted in an inflammatory response in the vagina characterized by neutrophils and infiltrating submucosal plasma cells consisting primarily of T cells. Despite the delayed clearance, rechallenged C. muridarum-infected mice were highly immune. Mice vaginally infected with C. muridarum produced serum and vaginal wash antibodies and an antigen-specific gamma interferon-dominated Th1-biased T cell response. By comparison, mice vaginally infected with C. trachomatis exhibited transient low-burden infections, produced no detectable tissue inflammatory response, and failed to seroconvert. We discuss how these marked differences in the biology of vaginal infection between these otherwise genetically similar species are possibly linked to pathogen-specific virulence genes and how they may influence pathology and immunity in the upper genital tract.
Insights
Chlamydia muridarum effectively infects mouse vaginal cells, causing a prolonged immune response, while Chlamydia trachomatis does not. This highlights species-specific differences in vaginal chlamydia infection and immunity.
Area of Science:
- Reproductive immunology
- Microbial pathogenesis
- Genital tract infections
Background:
- Chlamydia species are significant human and animal pathogens.
- Understanding Chlamydia infection dynamics in the lower genital tract is crucial for developing effective treatments and vaccines.
- Hysterectomized mouse models allow for the study of vaginal infections independent of upper genital tract influences.
Purpose of the Study:
- To compare the infectivity and immunogenicity of Chlamydia muridarum and Chlamydia trachomatis in the vaginal epithelium of hysterectomized mice.
- To investigate the host immune response to vaginal Chlamydia infection.
- To determine if differences in vaginal infection impact subsequent immunity.
Main Methods:
- Infection of hysterectomized mice with C. muridarum and C. trachomatis.
- Assessment of vaginal colonization and epithelial cell infection.
- Analysis of inflammatory cell infiltration in vaginal tissues.
- Measurement of serum and vaginal antibody responses.
- Evaluation of T cell responses, including gamma interferon production.
Main Results:
- C. muridarum readily infected vaginal squamous epithelial cells, establishing a prolonged infection.
- C. trachomatis failed to infect vaginal epithelial cells.
- C. muridarum infection induced a significant inflammatory response and a robust Th1-biased immune response with antibody production.
- Rechallenged C. muridarum-infected mice demonstrated strong immunity.
- C. trachomatis infection resulted in transient, low-burden infections with no detectable inflammatory or serological response.
Conclusions:
- Chlamydia muridarum and Chlamydia trachomatis exhibit distinct host-pathogen interactions within the vaginal epithelium.
- The ability of C. muridarum to infect vaginal cells is linked to a potent and protective immune response.
- Differences in virulence factors likely contribute to the divergent infection outcomes and immune responses observed between these Chlamydia species.
- These findings have implications for understanding the pathogenesis and immune control of Chlamydia infections in the upper genital tract.

