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

沙眼衣原体性传播感染（STI）是最常见的细菌性STI， 美国和世界范围内，并代表一个重大的公共卫生问题。目前没有 生物标志物可靠地预测潜在的破坏性衣原体相关的生殖并发症， 不孕症和宫外孕;因此，衣原体疫苗的开发是一个高度优先事项。的 衣原体感染或接种疫苗后“保护性免疫”的传统定义包括减少 细菌脱落，缩短感染持续时间，减少慢性组织损伤。但 保护性免疫的免疫学相关性不太明确，通常包括代 IgG抗体和强大的CD 4 + Th 1反应，尽管后者也与病理学有关 并且可能不足以作为免疫功效的单一读出。该项目的总体目标是 确定有助于衣原体有效产生的免疫和细胞反应 小鼠特异性免疫记忆我们假设CD 4+中枢和效应记忆 C.感染或免疫是一个关键的决定因素， 保护性免疫和/或病理学，并且作为推论，改变的IL-23/Th 17应答可能导致 CD 4 + T细胞记忆反应不足。采用一系列体内实验，在一个既定的 在小鼠模型中，我们的假设将通过以下具体目的进行测试：1）表征细胞和 与保护性CD 4+记忆T细胞应答的发展相关的免疫应答 生殖道衣原体感染后2)评估IL-23/Th 17的贡献 在产生有效的CD 4 + T细胞中枢和效应记忆反应的C.穆里达鲁姆 生殖道感染3)确定用杀死的微生物免疫是否会产生不同的记忆反应 自然感染。从拟议研究中获得的信息将促进项目负责人的 近期和长期的职业目标，以扩大她的技术和分析研究技能，发展 衣原体性传播感染后不良疾病结局的生物标志物，并将研究结果转化为基础研究。 免疫学实验室纳入临床相关性传播感染预防和干预战略。项目 领导者将把热情的指导与众多的机构资源相结合，以实现她的目标， 成为一名独立的研究者，在生殖道粘膜领域拥有既定的科学利基 免疫学

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.