Sexually transmitted infections (STI) with Chlamydia trachomatis are the most common bacterial STI in both the United States and worldwide and represent a significant public health concern. At present, there are no biomarkers to reliably predict potentially devastating Chlamydia-associated reproductive complications, such as infertility and ectopic pregnancy;therefore, development of a chlamydial vaccine is a high priority. The traditional definition of "protective immunity" following chlamydial infection or vaccination includes reduced bacterial shedding, shortened duration of infection, and diminished chronic tissue damage. However, the immunologic correlates of protective immunity are less well-defined and have generally included generation of IgG antibody and a robust CD4+ Th1 response although the latter has also been implicated in pathology and may not be adequate as a single read-out for immunologic efficacy. The overall goal of this project is to define the immunologic and cellular responses that contribute to effective generation of Chlamydia muridarum-specific immunologic memory. We hypothesize that the CD4+ central and effector memory phenotype elicited following C. muridarum Infection or immunization is a critical determinant of protective immunity and/or pathology and, as a corollary, that altered IL-23/Th17 responses may result in inadequate CD4+ T-cell memory responses. Employing a series of in vivo experiments in an established mouse model, our hypothesis will be tested by the following Specific Aims: 1) Characterize the cellular and immunologic responses associated with the development of protective CD4+ memory T-cell responses following Chlamydia muridarum genital tract infection. 2) Evaluate the contribution of the IL-23/Th17 response in generation of effective CD4+ T-cell central and effector memory responses to C. muridarum genital tract infection. 3) Determine if immunization with killed organisms elicits a different memory response than natural infection. Information gained from the proposed studies will advance the Project Leader's immediate and long-term career objectives to expand her technical and analytical research skills, develop biomarkers for adverse disease outcomes following Chlamydia STI, and translate findings in the basic immunology laboratory into clinically relevant prevention and intervention strategies for STI. The Project Leader will integrate enthusiastic mentorship with numerous institutional resources to reach her goal of becoming an independent investigator with an established scientific niche in genital tract mucosal immunology.
Sexually transmitted Chlamydia trachomatis infections are a significant public health problem due to their high frequency and risk of reproductive complications, including infertility and ectopic pregnancy. This project characterizes the immune response to chlamydial infection and immunization to determine the most effective regimens to protect from infection and chronic chlamydial disease.
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