Impact of microbial exposure on immune development

微生物暴露对免疫发育的影响

基本信息

批准号：
9789838
负责人：
Brian David Rudd
金额：
$ 46.53万
依托单位：
CORNELL UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-24 至 2021-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9789838
关键词：
ATAC-seq Adaptive Immune System Adult Affect Age Animals Asthma Birth CD8-Positive T-Lymphocytes CD8B1 gene Cell Compartmentation Cells Cellular Immunity Cytotoxic T-Lymphocytes Data Development Disease Elderly Environment Event Exhibits Exposure to Failure Genomic approach Goals Growth Hypersensitivity Immune Immune response Immune system Immunity Individual Infection Infection Control Inflammatory Inflammatory Bowel Diseases Insulin-Dependent Diabetes Mellitus Knowledge Label Life Link Listeria monocytogenes Mediating Microbe Molecular Mothers Mus Neonatal Peripheral Phenotype Play Positioning Attribute Predisposition Pregnancy Production Resistance Role Shapes Signal Transduction T cell response T-Cell Development T-Lymphocyte Testing arm cell behavior disorder risk fetal fetal loss germ free condition improved in utero innovation insight interest microbial microbial colonization microbiota migration mouse model novel offspring pathogen programs response tool transcriptome sequencing

项目摘要

Project Summary / Abstract The exposure to microbes in utero and after birth permanently programs an individual’s immune system and life- long disease risk. However, the relationship between microbial exposure and immune ontogeny remain poorly defined. We have developed a mouse model to better understand how the maternal microbial environment shapes the offspring’s immune system. Our preliminary data indicates that the timing of microbial exposure has a profound impact on susceptibility to intracellular pathogens later in life. Thus, a main objective of this proposal is to dissect out how maternal microbial exposure alters the development and function of the offspring’s CD8+ T cells. To accomplish this objective, we will use a number of cutting-edge approaches to test the hypothesis that microbial exposure programs immune susceptibility by altering the developmental layers of the CD8+ T cell response to infection. In the first, aim we will determine how microbial exposure changes the way the CD8+ T cell compartment is ‘put-together.’ Results from this aim will provide insight into how the composition and programming of CD8+ T cells in the offspring are linked to microbial exposure in the earliest days of life. In the second aim, we will examine how the amount and timing of microbial exposure alter the offspring’s response to intracellular pathogens. We are particularly interested in determining how microbial exposure during specific windows of development (in utero, post-natal) changes the offspring’s CD8+ T cell response to infection later in life. Our proposal aims to provide a new conceptual framework for understanding how microbial colonization in early life leads to life-long, potentially irreversible, changes in the offspring’s immune system. Knowledge gained from these studies is expected to broaden our fundamental understanding of immune development and cell- mediated immunity.

项目概要/摘要在子宫内和出生后接触微生物会永久地影响个体的免疫系统和生命。然而，微生物暴露与免疫个体发育之间的关系仍然很差。我们开发了一种小鼠模型，以更好地了解母体微生物环境的定义。我们的初步数据表明微生物暴露的时间已经影响了后代的免疫系统。对生命后期对细胞内病原体的易感性产生深远影响，因此，这是该提案的一个主要目标。目的是剖析母体微生物暴露如何改变后代 CD8+ T 的发育和功能为了实现这一目标，我们将使用许多尖端方法来检验以下假设：微生物暴露通过改变 CD8+ T 细胞的发育层来调节免疫易感性首先，我们将确定微生物暴露如何改变 CD8+ T 的方式。细胞室是“组合在一起的”。这一目标的结果将深入了解细胞室的组成和结构如何后代 CD8+ T 细胞的编程与生命早期接触微生物有关。第二个目标，我们将研究微生物暴露的数量和时间如何改变后代的反应我们特别感兴趣的是确定特定期间微生物的暴露情况。发育窗口（子宫内、产后）会改变后代的 CD8+ T 细胞对感染的反应我们的建议旨在提供一个新的概念框架来理解微生物定植是如何发生的。早期生命会导致后代免疫系统发生终生的、可能不可逆转的变化。这些研究预计将拓宽我们对免疫发育和细胞的基本理解。介导的免疫。