A spatial transcriptional analsysis of Chlamydia-mediated upper genital tract pathology

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Chlamydia trachomatis is the most common sexually transmitted bacterial pathogen. C. trachomatis infections can ascend to the female upper genital tract (UGT) leading to acute and chronic infections than cause pelvic inflammatory disease and fallopian tube scarring. These inflammatory pathologies have a large negative impact on women’s reproductive health. We know remarkably little as to the cellular and molecular processes underlying acute and chronic infections of the UGT, and how they promote permanent tissue damage even long after the pathogen has been cleared. Similarly, what role Chlamydia virulence factors play in this process is largely unknown. In this application we propose to apply emerging transcriptional profiling technologies to catalogue the cellular and gene expression events from initial infection, to resolution, to fibrotic damage post bacterial clearance at single cell resolution in the female UGT following a challenge with Chlamydia muridarum, a mouse adapted Chlamydia sp. In addition, to understand the mechanisms underlying the emergence of fibrosis and how long-lasting tissue damage that can lead to infertility, we will compare cellular responses in the UGT and their corresponding single-cell gene expression profiles upon challenges with Chlamydia mutants that cause altered pathologies. These longitudinal studies will define the types of cells that drive Chlamydia-dependent inflammatory damage and provide new insight as to how the spatial distribution of these cells correlate with pathogen clearance and pathology. Furthermore, the proposed studies will provide a unique resource for the characterization of inflammatory processes and fibrotic damage in an organ of significant importance for reproductive health.