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Project 2 - Regulation of the T-cell Memory Response in Chlamydia Genital Tract

项目 2 - 衣原体生殖道 T 细胞记忆反应的调节

基本信息

批准号：
8460760
负责人：
AMY M. SCURLOCK
金额：
$ 33.07万
依托单位：
UNIV OF ARKANSAS FOR MED SCIS
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/8460760
关键词：
Adverse effects Antibodies Biological Markers CD4 Positive T Lymphocytes Cells Centers of Research Excellence Cervical Chlamydia Chlamydia Infections Chlamydia muridarum Chlamydia trachomatis Chronic Data Development Disease Disease Outcome Ectopic Pregnancy Environment Event Female Fostering Frequencies Future Generations Genital system Goals Hour Immune Immune response Immunity Immunization Immunoglobulin G Immunologic Memory Immunologics Immunology Individual Infection Infection prevention Infertility Inflammatory Response Interleukin-17 Intervention Kinetics Laboratories Life Link Mediating Mediator of activation protein Memory Mentorship Metric Molecular Mus Natural Immunity Organism Pathogenesis Pathology Pelvic Inflammatory Disease Phenotype Play Prevalence Prevention strategy Public Health Publishing Reading Recruitment Activity Regimen Regulation Reproduction Research Research Personnel Resources Risk Role Route Screening procedure Series Sexually Transmitted Diseases Surrogate Markers T cell response T memory cell Testing Th1 Cells Therapeutic Tissues Translating United States Vaccination Vaccines adaptive immunity career chemokine clinically relevant cytokine genital infection high risk human subject improved in vivo interleukin-23 killings meetings memory CD4 T lymphocyte microbial mouse model prevent programs reproductive research study response skills translational study vaccine development vaccine-induced immunity

项目摘要

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.

沙眼衣原体性传播感染是两国最常见的细菌性传播感染