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Role of gut microbiota-induced IgG in enteric host defense

肠道微生物诱导的 IgG 在肠道宿主防御中的作用

基本信息

批准号：
9526198
负责人：
Melody Y Zeng
金额：
$ 10.98万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
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：
2018-04-01 至 2018-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9526198
关键词：
Antibodies Antigens Bacteria Breast Feeding Citrobacter Citrobacter rodentium Communicable Diseases Ensure Enteral Environment Escherichia coli EHEC Foundations Gnotobiotic Grant Health Host Defense Human Human Milk Human body Immune response Immune system Immunization Immunoglobulin G Infection Intestines Investigation Learning Life Mediating Mentors Metabolism Michigan Mission Modeling Moon Morbidity - disease rate Mucous Membrane Mus Neonatal Newborn Infant Nutrient Play Pregnancy Premature Infant Research Role Scientist Sepsis Solid Supervision Symbiosis Systemic infection Testing Therapeutic Training United States National Institutes of Health Universities Vaccines Work career development field study gut bacteria gut microbiota immune resistance improved insight metabolomics mortality nanoparticle neonatal immunity neonatal sepsis neonate novel novel strategies pathogen preterm newborn programs skills therapeutic development vaccine trial

项目摘要

Project Summary/Abstract The gut microbiota has a plethora of important functions that promote human health. The impact of maternal gut microbiota on neonatal health, however, remains largely unknown. Sepsis is an important cause of morbidity and mortality among newborn infants, particularly in preterm infants. Our preliminary studies have unraveled a previously unknown function of the gut microbiota to induce antigen-specific IgG antibodies under homeostatic conditions, which can rapidly mediate clearance of pathogens bearing conserved IgG antigens during systemic infection. Importantly, we found robust levels of commensal-specific IgG antibodies in both mouse and human breast milk. Therefore, our central hypothesis is that 1) maternal commensal IgG confers critical protection to the neonate against infection; 2) maternal immunization with IgG-inducing beneficial gut symbiotic bacteria, or IgG-inducing antigens, may be a novel approach to treat neonatal sepsis, which can be caused by dissemination of gut bacteria. This hypothesis will be tested through three specific aims: 1) determine the role of maternal gut microbiota-induced IgG in neonatal enteric infection, 2) identify and characterize gut symbiotic bacteria that induce homeostatic antigen-specific IgG antibodies, and 3) determine whether maternal immunization with IgG-inducing bacteria or antigens confers protection in the neonate. The objective of the current application is to harness gut microbiota-induced IgG to develop therapeutics for neonatal sepsis, and for the PI to learn new skills such as developing neonatal infection models and vaccine nanoparticles, which are important for her to develop an independent research program with a focus on the gut microbiota and neonatal health. The research is significant because these studies will unravel potentially novel and effective approaches to treat neonatal sepsis. The distinguished mentoring team will allow the PI to complete the proposed studies with new skills and transition to independence in a new field of study. In addition, the excellent research environment of the University of Michigan will provide exceptional support for the proposed studies and the PI's career development.

项目总结/文摘