The role of myeloid cells in the female genital tract during chlamydial infection – possible impact on control of chlamydia and on inflammation-induced tissue damage

• Applicant: Privatdozentin Dr. Susanne Kirschnek
• Subject Area: Immunology ; Medical Microbiology and Mycology, Hygiene, Molecular Infection Biology
• Term: since 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 456376522

The obligate intracellular bacterium Chlamydia (C.) trachomatis is the most common bacterial agent of sexually transmitted disease world-wide. Since most genital C. trachomatis infections are subclinical in women and thus remain untreated, infection may in some cases develop into chronic disease, resulting in pelvic inflammatory disease (PID) with fibrotic scarring and serious consequences such as infertility and ectopic pregnancy. The immune system probably plays an important role in pathogenesis of these long-term sequelae. We have an established mouse model of chlamydial genital infection with C. muridarum in our lab. Our previous in vitro and in vivo data demonstrate a certain role for neutrophil granulocytes in the development of late-stage tissue damage, but also indicate a massive and long-lasting infiltration of other myeloid cells (monocytic and dendritic cells) during the course of infection, the impact of which ist still mostly unclear. This project aims to identify the role of myeloid cells in the innate immune response to genital chlamydial infection and to clarify their relevance for bacterial clearance, establishment of chronic infection and development of long-term tissue damage. We will at first identify and functionally characterize subpopulations of mononuclear phagocytes in the female genital tract at steady-state and during chlamydial infection. In addition, we will analyse the spatio-temporal contribution of myeloid cell populations to the ascencion of chlamydia to the upper genital tract, establishment of long-term infection and development of tissue damage by high-resolution microscopy complemented by further independent methods. In the third part, we will investigate the role of the cryptic chlamydial plasmid (an important virulence factor present in almost all pathogenic chlamydia isolates which carries 8 ORFS with still mostly unknown function) with respect to the myeloid immune response to chlamydial infection. We believe that this work may a basis for potential future targeting of myeloid cells by modulation of their survival and activity. This may reveal new therapeutic options for prevention of irreparable tissue damage caused by chronic chlamydial infection, but may also contribute to a better understanding of other diseases in the female genital tract where myeloid cells have potential regulatory roles.

• DFG Programme: Research Grants