Abstract
Chlamydia trachomatis, a leading bacterial cause of sexually transmitted infection-induced infertility, is frequently detected in the gastrointestinal tract. Chlamydia muridarum, a model pathogen for investigating C. trachomatis pathogenesis, readily spreads from the mouse genital tract to the gastrointestinal tract, establishing long-lasting colonization. C. muridarum mutants, despite their ability to activate acute oviduct inflammation, are attenuated in inducing tubal fibrosis and are no longer able to colonize the gastrointestinal tract, suggesting that the spread of C. muridarum to the gastrointestinal tract may contribute to its pathogenicity in the upper genital tract. However, gastrointestinal C. muridarum cannot directly autoinoculate the genital tract. Both antigen-specific CD8(+) T cells and profibrotic cytokines, such as TNFα and IL-13, are essential for C. muridarum to induce tubal fibrosis; this may be induced by the gastrointestinal C. muridarum, as a second hit, to transmucosally convert tubal repairing - initiated by C. muridarum infection of tubal epithelial cells (serving as the first hit) - into pathogenic fibrosis. Testing the two-hit mouse model should both add new knowledge to the growing list of mechanisms by which gastrointestinal microbes contribute to pathologies in extragastrointestinal tissues and provide information for investigating the potential role of gastrointestinal C. trachomatis in human chlamydial pathogenesis.