The immunological determinants of protective immunity and immunopathology in human Chlamydia trachomatis infection. (360G-Wellcome-093368_Z_10_Z)

The goal of this programme is to determine the immunological and molecular basis of protection and pathology following exposure to ocular Chlamydia trachomatis (Ct) infection in humans. We aim to test the relevance of hypotheses concerning interactions between Ct and the host, generated in vitro and in animal models, in naturally infected human subjects. This will enable us to define rational strategies for vaccine development and delivery, and to determine whether immune responses to candidate vaccines are likely to be protective or damaging. We hypothesise that the resolution of chlamydial infection without associated tissue damage depends on the balance between pro-inflammatory innate immune responses, host responses that act to limit chlamydial replication, and those homeostatic mechanisms induced in parallel which limit inflammation, thereby reducing the potential for tissue damage, but which may be more permissive to chlamydial replication and persistence. We will study the rel ationship between immune responses (in the peripheral blood and at the site of infection) and the clinical and microbiological outcomes of infection in a cohort study, and identify genetic polymorphisms associated with adverse outcomes by case-control and family-based association studies in trachoma endemic populations.