Immunoregulatory Networks in Chlamydia Genital Tract Infection

描述（由申请人提供）：Amy Scurlock，医学博士，她是一名助理教授，于2004年完成了过敏/免疫学奖学金。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，将通过整合她的经验丰富的赞助商，博士的热情指导来扩大她的科学技能。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STI，是一个重大的公共卫生问题。目前，还没有生物标志物可以预测与衣原体感染相关的潜在破坏性生殖并发症，例如不孕症和宫外孕。该研究计划将评估衣原体感染后效应和调节CD 4 + T细胞反应的多样性。中心假说提出，CD 4 + Th 17谱系是一种病理性CD 4+效应反应，促进生殖道衣原体感染后的生殖道病理。在建立的小鼠模型中采用一系列体内实验，通过以下特定目的来检验该假设：1）确定Th 17应答在衣原体生殖道感染后生殖道病理学发展中的作用，2）检查Th 17和T调节细胞在调节衣原体生殖道感染结果中的相互作用。从拟议的研究中获得的信息将推进Scurlock博士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临床相关的STI预防和干预策略。PI将利用阿肯色州大学医学科学和阿肯色州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，以实现她成为一名独立研究者的目标，并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，因为它们的高频率和生殖并发症，包括不孕症和异位妊娠的风险。该项目评估了新描述的T辅助细胞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.