Gestation Dependent Immune Response to Group B Streptococcus Infection During Pregnancy

妊娠期间 B 族链球菌感染的妊娠依赖性免疫反应

基本信息

批准号：
10644769
负责人：
Kristen Nicole Noble
金额：
$ 14.92万
依托单位：
VANDERBILT UNIVERSITY MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-06-01 至 2028-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10644769
关键词：
Academic Medical Centers Acute Anti-Inflammatory Agents Bacterial Infections CD80 gene Cells Chronic Disease Clinical Collaborations Cytometry Data Depressed mood Diagnostic Diphtheria Toxin Embryo Environment Evolution Faculty Fetal Membranes Fetal health Fetus First Pregnancy Trimester Genetic Genetic Transcription Gestational Age Goals High-Risk Pregnancy Host Defense Human IL8 gene Immune Immune Tolerance Immune response Immune system Immunity Immunofluorescence Immunologic Immunologics In Situ Infection Inflammatory Innate Immune Response Innate Immune System Interleukin-6 K-Series Research Career Programs Knowledge Literature Macrophage Maternal and Child Health Maternal-Fetal Exchange Mentors Mentorship Modeling Mus Natural Immunity Nature Neonatology Organ Outcome PTPRC gene Pathologic Persons Phenotype Physicians Placenta Placentation Population Pregnancy Pregnancy Outcome Premature Birth Preventive Publications Reproductive Immunology Research Resolution Resource Sharing Role Running Scientist Severities Signal Transduction Streptococcal Infections Streptococcus Group B Surface Systems Biology TNF gene Techniques Technology Testing Therapeutic Third Pregnancy Trimester Time Tissues Training Transgenic Organisms Uterus Vagina career career development cytokine diagnostic biomarker disability fetal fighting first responder improved instructor intraamniotic infection monocyte mouse model multidisciplinary next generation sequencing novel diagnostics novel therapeutic intervention offspring pathogen placental membrane pregnant programs recruit reproductive response single-cell RNA sequencing skills stillbirth

项目摘要

PROJECT SUMMARY The goal of this Mentored Clinical Scientist Research Career Development Award is to provide the necessary training and skills to develop into a physician scientist who successfully runs an independent research program focused on reproductive immunology. Dr. Kristen Noble is an Instructor in the Division of Neonatology at Vanderbilt University Medical Center. Her career goal is to study the host response to infection during pregnancy to develop novel diagnostic and therapeutic strategies to improve maternal-fetal health. With the strong mentorship of Dr. C. Henrique Serezani, Dr. David Aronoff, and a multidisciplinary Faculty Oversight Committee, Dr. Noble will master skills in systems biology (including next generation sequencing and ultra-high level multiplex immunofluorescence), modeling of infection during pregnancy, and techniques in reproductive immunology. Vanderbilt provides a rich environment for scientific discovery and collaboration with unique career development opportunities, shared resources, and facilities with cutting-edge technology to support early career physician-scientists on their path to independence. This proposal tests the central hypothesis that the natural evolution of the immune system during pregnancy dictates gestation-dependent pregnancy outcomes to Group B Streptococcal (GBS) infection, including differential maternal and fetal immune responses in the gestational tissues. To test this hypothesis, Aim 1 will define dynamic genetic programs at the single cell level that are activated in response to GBS infection as a function of gestational age. The intrauterine gestational tissues have unique and dynamic immune compositions throughout pregnancy. Therefore, we will also use ultra-high level multiplex immunofluorescence to provide spatial context to key GBS-induced immune responses. The innate immune system is essential for the protection against pathogens. The intrauterine niche is uniquely composed of both maternal- and fetal- derived innate immune cells, including macrophages. Aim 2 will use unique mouse models to define the differential maternal and fetal macrophage contributions to immunity against GBS and to pregnancy outcomes after infection. Completion of these aims will close substantial knowledge gaps regarding the dynamic nature of local intrauterine immunity protecting against bacterial infection during pregnancy. This is critical for the discovery of early diagnostic indicators of infection of which there are none, and necessary to identify potential therapeutic mechanisms for decreasing poor pregnancy outcomes after GBS infection.

项目概要该指导临床科学家研究职业发展奖的目标是提供必要的培养成为成功开展独立研究项目的医师科学家的培训和技能专注于生殖免疫学。 Kristen Noble 博士是新生儿科的讲师范德比尔特大学医学中心。她的职业目标是研究宿主对感染的反应妊娠期制定新的诊断和治疗策略以改善母婴健康。随着 C. Henrique Serezani 博士、David Aronoff 博士的强有力指导以及多学科的教师监督委员会主席，Noble 博士将掌握系统生物学技能（包括下一代测序和超高水平多重免疫荧光）、妊娠期间感染建模以及生殖技术免疫学。范德比尔特大学以独特的方式为科学发现和合作提供了丰富的环境职业发展机会、共享资源以及具有尖端技术的设施支持早期职业医师科学家走上独立之路。该提案检验了怀孕期间免疫系统自然进化的中心假设决定了 B 族链球菌 (GBS) 感染与妊娠相关的妊娠结局，包括妊娠组织中母体和胎儿免疫反应的差异。为了检验这个假设，目标 1 将将响应 GBS 感染而激活的单细胞水平的动态遗传程序定义为胎龄的函数。宫内妊娠组织具有独特的动态免疫功能整个怀孕期间的成分。因此，我们还将使用超高水平多重免疫荧光为 GBS 诱导的关键免疫反应提供空间背景。先天免疫系统对于针对病原体的保护。子宫内生态位独特地由母体和胎儿组成衍生的先天免疫细胞，包括巨噬细胞。 Aim 2 将使用独特的鼠标模型来定义母体和胎儿巨噬细胞对 GBS 免疫力和妊娠结局的不同贡献感染后。完成这些目标将弥补有关动态性质的巨大知识差距局部宫内免疫可防止怀孕期间的细菌感染。这对于发现尚无感染的早期诊断指标，并且有必要识别潜在的感染指标减少 GBS 感染后不良妊娠结局的治疗机制。