Gastrointestinal co-infection promotes chlamydial pathogenicity in the genital tract.

Sexually transmitted Chlamydia, which can cause fibrotic pathology in women9s genital tracts, is also frequently detected in the gastrointestinal tract. However, the medical significance of the gastrointestinal Chlamydia remains unclear. A murine Chlamydia readily spreads from mouse genital to gastrointestinal tract while inducing oviduct fibrotic blockage or hydrosalpinx. We previously proposed a 2-hit model in which the mouse gastrointestinal Chlamydia might induce the 2nd hit to promote genital tract pathology and we are now providing experimental evidence for testing the hypothesis. First, chlamydial mutants that are attenuated in inducing hydrosalpinx in the genital tract also reduce their colonization in the gastrointestinal tract, leading to a better correlation of chlamydial induction of hydrosalpinx with chlamydial colonization in the gastrointestinal tract than the genital tract. Second, intragastric co-inoculation with a wild type Chlamydia rescued an attenuated Chlamydia mutant to induce hydrosalpinx while the chlamydial mutant infection in the genital tract alone was unable to induce any significant hydrosalpinx. Finally, the co-inoculated gastrointestinal Chlamydia failed to directly spread to the genital tract lumen, suggesting that gastrointestinal Chlamydia may promote genital pathology via an indirect mechanism. Thus, we have demonstrated a significant role of gastrointestinal Chlamydia in promoting pathology in the genital tract possibly via an indirect mechanism. This study has provided a novel direction/dimension for further investigating chlamydial pathogenic mechanisms.