Immunoregulatory Networks in Chlamydia Genital Tract Infection

简介(申请人提供)：艾米·斯柯洛克，医学博士，助理教授，2004年完成过敏/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，该计划将通过将她的经验丰富的赞助人Roger Rank博士和科学咨询委员会的热情指导与众多机构资源相结合来扩展她的科学技能。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，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器和调节性CD4T细胞反应的不断扩大的多样性。中心假说认为，在衣原体生殖道感染后，CD4Th17谱系是一种病理性的CD4效应器反应，促进生殖道病理。通过在已建立的小鼠模型中进行的一系列体内实验，将通过以下特定目的来检验这一假说：1)确定Th17反应在衣原体生殖道感染后生殖道病理发展中的作用；2)检查Th17与T调节细胞在调节衣原体生殖道感染结局方面的相互作用。从拟议的研究中获得的信息将推动斯柯洛克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，开发针对性病衣原体感染后不良疾病后果的生物标记物，并将基础免疫学实验室的研究结果转化为与临床相关的性病预防和干预策略。PI将利用阿肯色大学医学科学大学和阿肯色州儿童医院研究所强大的指导、受保护的研究时间和出色的学术资源来实现她的目标，即成为一名在生殖道粘膜免疫学领域拥有既定科学地位的独立研究员。相关性：性传播沙眼衣原体感染是一个重大的公共卫生问题，因为它们的频率很高，而且有可能出现生殖并发症，包括不孕不育和宫外孕。该项目评估了新描述的T辅助分子17反应是衣原体引起的生殖道组织损伤的重要因素。

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.