权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Immune interactions with commensal microbes in early life

生命早期与共生微生物的免疫相互作用

基本信息

批准号：
10567936
负责人：
CHYI S HSIEH
金额：
$ 71.52万
依托单位：
WASHINGTON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-11-02 至 2027-10-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10567936
关键词：
Address Adult Affect Allergic Antibiotics Antigen Presentation Antigen-Presenting Cells Antigens Bacteria Bacterial Antigens Bacterial Infections Bacterial Translocation Biological Bypass CD4 Positive T Lymphocytes Cells Colitis Colon Data Development Disease Distant Elderly Event Future Generations Genetic Germ-Free Goblet Cells Growth Helicobacter Homeostasis Human Hygiene Immune Immune System Diseases Immune response Immune system Immunologic Stimulation In Vitro Individual Infection Inflammatory Bowel Diseases Inflammatory Response Intestines Knowledge Laboratories Lactobacillus Lamina Propria Life Lymphoid Tissue Measures Mediating Methods Microbe Mus Nature Outcome Pathologic Pathology Pathway interactions Pattern Peripheral Phase Phenotype Physiological Population Predisposition Reagent Regulatory T-Lymphocyte Reporting Reproducibility Resistance Risk Risk Factors Role Route Severities Small Intestines System T cell response T-Lymphocyte T-cell receptor repertoire Testing Time Transgenic Mice Transgenic Organisms Weaning antigen-specific T cells commensal bacteria commensal microbes feeding gut bacteria gut homeostasis gut microbiota immune function immune health in vivo mesenteric lymph node microbial microbiota pharmacologic prevent response single-cell RNA sequencing

项目摘要

Project Summary/Abstract Events in early life, particularly those altering the gut microbiota and immune development, can have an important role in determining future risk of immune related disorders. For example, it has been reported that the how substances are encountered by the immune system, the timing of feeding practices, hygiene, and the use of antibiotics, in early life can modify the risk of immune driven disorders later in life. A common theme amongst many of these studies is that these risk factors likely affect the developing microbiota. However, the biologic basis for how early life microbial changes can affect the risk of immune disorders later in life is incompletely understood. Previous data from our laboratories have suggested that during this preweaning period, specific live gut bacteria are selectively delivered to the immune system and that interaction of these live bacteria with cellular immune populations locally in the colonic lamina propria or in distant lymphoid tissues establishes a durable (life- long) and balanced immune system. In preliminary studies, we observed substantial variance in the amount of bacterial translocation in this preweaning period, which was corroborated with studies of antigen-specific T cell responses to a translocating bacterial spp. We therefore hypothesize that the magnitude and quality of the immune response to these translocating bacteria species during the preweaning period is a stochastic event during normal ontogeny which represents an important variable in determining whether an individual establishes a balanced immune system and prevents immune mediated pathologies in later life. However, the nature of these translocating bacteria and methods to quantify the antigen-specific responses to these bacteria remain a gap in our knowledge. We will address this question by identifying and characterizing how the translocating bacteria are encountered by the immune system (Aim 1) and generate reagents to track bacterial antigen presentation via T cell responses in vivo (Aim 2). We will use these reagents to integrate the immune response over the preweaning period to translocating bacterial spp. during physiologic development and correlate it with intestinal immune challenges including infection and experimental colitis in later life (Aim 3). If successful, this project may reveal that preweaning translocation is an important stochastic developmental variable involved in generating intestinal immune health and homeostasis.

项目总结/文摘