Project B01

Mechanisms driving chlamydial persistence and ascending infection in the female reproductive tract

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Prof. Dr. Thomas Rudel

 

Chlamydia trachomatis (Ctr) causes infections of the lower (cervix) and occasionally also the upper (fallopian tubes) female reproductive tract (FRT). Irrespective of the localisation of the infection focus, the bacteria can shift from acute to persistent infection. This shift may be connected to chronic diseases, including pelvic inflammatory disease, infertility and cervical and ovarian cancer. This project aims to understand how persistent Chlamydia infection is established after initial contact of Ctr with heterogeneous epithelial cell (sub)types of the lower and upper FRT. Based on our preliminary data, we hypothesise that certain epithelial cell (sub)types promote, while others restrict chlamydial replication. The local immune response mounted by infiltrating immune cells changes the physiology of the epithelial cells and thereby also the metabolic environment. As a consequence, Ctr persistence is induced even in epithelial cells that are initially replication permissive. Herpesvirus co-infection, which has been identified as a strong inducer of chlamydial persistence, has a similar effect. We will identify molecular decision points that determine the switch from productive to persistent Chlamydia infection in these infection scenarios. In addition, we hypothesise that specific subpopulations of immune cells that are mounting the local immune response in the infected epithelia may take up the bacteria and transport them to the upper female genital tract as a mechanism of ascending infection. A long-term goal will be the mechanistic understanding of molecular decision points for spatial and time resolved development of ascending and persistent Ctr infection in the FRT as the basis for new therapeutic approaches.