Chlamydia infections are a major cause of sexually transmitted disease in the US. Greater understanding of protective immunity to Chlamydia at mucosal surfaces is urgently required if an effective vaccine is to become a reality. This application proposes to develop a TCR transgenic mouse to uncover fundamental aspects of mucosal CD4 T cell biology during infection of the reproductive tract with Chlamydia. Our experimental approach is unique in that it will utilize a natural route of infection, an establishe mouse model of infection where CD4 T cells participate in pathogen clearance, and involve direct visualization of pathogen-specific CD4 T cells using reagents and techniques that we will develop. Our application specifically proposes to, (i) identify antigen presenting cell subsets tha drive CD4 T effector cell priming in the reproductive tract, and (ii) define the heterogeneity of te CD4 T cell memory pool required for protective immunity in the upper reproductive tract. Understanding both these issues will be vitally important for the generation of a vaccine against Chlamydia, one of the most important pathogens affecting the reproductive health of young women in the US.
Chlamydia trachomatis causes blindness worldwide and is responsible for an extremely large number of sexually transmitted infections in the US. The CDC estimates that Chlamydia is one of the most prevalent bacterial infections in the US and the consequences of infection afflict otherwise healthy young women. Unfortunately, women with untreated Chlamydia infection can develop serious pelvic inflammatory disease (PID), infertility, chronic pelvic pain, or suffer ectopic pregnancy. Given the incidence of infection and the potential for serious pathology, the current consensus among scientists and clinicians is that an effective Chlamydia vaccine is needed. In order for a vaccine to be generated, greater understanding of host immunity to Chlamydia infection in the upper reproductive tract is required. Our application will develop and utilize new antigen-specific reagents that will facilitae detailed examination of CD4 T cells in a mouse model of genital Chlamydia infection.
