Immunoregulatory Networks in Chlamydia Genital Tract Infection

描述（由申请人提供）：Amy Scurlock，医学博士，是一名助理教授，她于2004年完成了过敏/免疫学研究。在这份申请中，她描述了一个多方面的、为期5年的研究和教育培训计划，通过将她经验丰富的赞助人罗杰·兰克博士的热情指导和科学咨询委员会与众多机构资源相结合，该计划将扩展她的科学技能。沙眼衣原体性传播感染（STI）是美国和世界范围内最常见的细菌性传播感染，是一个重大的公共卫生问题。目前，还没有生物标志物来预测与衣原体感染相关的潜在破坏性生殖并发症，如不孕症和异位妊娠。该研究计划将评估衣原体感染后效应和调节性CD4+ t细胞反应的扩大多样性。中心假设提出CD4+ Th17谱系是一种病理性CD4+效应反应，在衣原体生殖道感染后促进生殖道病理。通过建立小鼠模型的一系列体内实验，我们将通过以下具体目的来验证这一假设：1)确定Th17应答在衣原体生殖道感染后生殖道病理发展中的作用；2)研究Th17与t调节细胞在衣原体生殖道感染结局中的相互作用。从拟议的研究中获得的信息将推进她的近期和长期职业目标，以扩大她的技术和分析研究技能，开发衣原体STI后不良疾病结果的生物标志物，并将基础免疫学实验室的发现转化为STI的临床相关预防和干预策略。PI将利用阿肯色大学医学科学学院和阿肯色儿童医院研究所的强大指导、受保护的研究时间和优秀的学术资源，实现她成为一名独立研究者的目标，在生殖道粘膜免疫学领域建立科学利基。相关性：性传播的沙眼衣原体感染是一个重大的公共卫生问题，因为其高频率和风险的生殖并发症，包括不孕症和异位妊娠。该项目评估了新描述的t -辅助性17反应作为衣原体诱导的生殖道组织损伤的重要贡献者。

DESCRIPTION (provided by applicant): Amy Scurlock, M.D., is an Assistant Professor who completed her Allergy/Immunology Fellowship in 2004. In this application, she describes a multi-faceted, 5-year research and educational training program that will expand her scientific skills by integrating the enthusiastic mentorship of her experienced sponsor, Dr. Roger Rank, and scientific advisory committee with numerous institutional resources. 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 predict potentially devastating reproductive complications, such as infertility and ectopic pregnancy, associated with Chlamydia infections. The research plan will evaluate the expanding diversity of effector and regulatory CD4+ T-cell responses following Chlamydia infection. The central hypothesis proposes that the CD4+ Th17 lineage is a pathologic CD4+ effector response that promotes reproductive tract pathology following Chlamydia genital tract infection. Employing a series of in vivo experiments in an established mouse model, the hypothesis will be tested by the following Specific Aims: 1) Determine the role of the Th17 response in development of reproductive tract pathology following chlamydial genital tract infection, 2) Examine the interaction between Th17 and T-regulatory cells in modulating the outcome of Chlamydia genital tract infection. Information gained from the proposed studies will advance Dr. Scurlock'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 PI will take advantage of strong mentoring, protected research time, and outstanding academic resources at the University of Arkansas for Medical Sciences and the Arkansas Children's Hospital Research Institute to reach her goal of becoming an independent investigator with an established scientific niche in genital tract mucosal immunology. RELEVANCE: 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 evaluates the newly described T-helper 17 response as an important contributor to Chlamydia-induced reproductive tract tissue damage.