Chlamydia trachomatis is the most frequently detected agent of sexually transmitted infections worldwide. Infection of the lower female genital tract (FGT) can cause cervicitis and if ascending to the upper FGT may result in serious sequelae such as pelvic inflammatory disease (PID), salpingitis and tubal factor infertility (TFI). The factors leading to this complication are still not completely understood. We elaborate four different models for host-pathogen interactions in C. trachomatis infections that may promote disease development: (1) acute infection, (2) repeated infections, (3) chronic/persistent infections and (4) non-inflammatory colonization. Whereas experimental data exist for all of these models in vitro, ex vivo and in vivo, we were interested in seeing what clinical evidence we have supporting one or the other model. We particularly focused on data that favour the one or the other model for TFI development in C. trachomatis infection and speculate on future studies that could integrate in vitro findings for a better characterization of the situation in vivo.

Genital tract infections with Chlamydia trachomatis (C. trachomatis) are the most frequent sexually transmitted disease worldwide. Severe clinical sequelae such as pelvic inflammatory disease (PID), tubal occlusion, and tubal infertility are linked to inflammatory processes of chronically infected tissues. The oxygen concentrations in the female urogenital tract are physiologically low and further diminished (0.5–5% O2, hypoxia) during an ongoing inflammation. However, little is known about the effect of a low oxygen environment on genital C. trachomatis infections. In this study, we investigated the host immune responses during reactivation of IFN-γ induced persistent C. trachomatis infection under hypoxia. For this purpose, the activation of the MAP-kinases p44/42 and p38 as well as the induction of the pro-inflammatory cytokines IL-1β, IL-6, IL-8, and MCP-1 were analyzed. Upon hypoxic reactivation of IFN-γ induced persistent C. trachomatis infection, the phosphorylation of the p44/42 but not of the p38 MAP-kinase was significantly diminished compared to IFN-γ induced chlamydial persistence under normoxic condition. In addition, significantly reduced IL-6 and IL-8 mRNA expression levels were observed for reactivated Chlamydiae under hypoxia compared to a persistent chlamydial infection under normoxia. Our findings indicate that hypoxia not only reactivates IFN-γ induced persistent C. trachomatis infections resulting in increased bacterial growth and progeny but also dampens inflammatory host immune signaling responses that are normally observed in a normoxic environment.