Regulation of early life immunity by maternal microchimeric cells

母体微嵌合细胞对生命早期免疫的调节

基本信息

批准号：
10561696
负责人：
Nitya Jain
金额：
$ 24.86万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
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：
2022-02-03 至 2024-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10561696
关键词：
Address Adult Affect Animal Model Antigens Bacterial Infections Biological Process Birth COVID-19 pandemic Cells Cessation of life Child Cohort Studies Communicable Diseases Development Disease Doctor of Philosophy Engraftment Epstein-Barr Virus Infections Fetal Development Fetus Human Human Milk Immune Immune response Immune system Immunity Immunization Immunize Immunoglobulin A Immunoglobulin G Immunologics Infant Infant Mortality Infection Infection prevention Knowledge Life Malaria Maternal antibody Maternally-Acquired Immunity Mediating Microchimerism Molecular Mothers Mus Nature Neonatal Newborn Infant Pathogenesis Pathway interactions Pneumonia Population Predisposition Pregnancy Pregnant Women Property Regulation Reporting Research Resistance Role Salmonella infections Sepsis Spleen T-Lymphocyte Technology Term Birth Testing Tetanus Tetanus Toxoid Thymus Gland Time Tissues Transfer Factor Vaccination Vaccines arm chronic infection disorder risk experience experimental study functional plasticity immune activation immune function immunoregulation imprint insight interest malaria infection maternal vaccination microbial mortality mouse model mutant neonatal death novel novel therapeutics offspring offspring immunity pathogen placental malaria preterm newborn response stem success tool trafficking transmission process vaccine response

项目摘要

PI/PD: Jain, Nitya Ph.D. PROJECT SUMMARY Early life immunity develops and matures over a period of time, leaving newborns susceptible to adverse microbial encounters. Indeed, bacterial infections are a major cause of mortality in preterm and term newborns. Protective maternal factors transferred to offspring are a crucial line of defense during this vulnerable period. One arm of this protection arises from engrafted maternal microchimeric cells (MMCs) that are transferred into the offspring during pregnancy. In humans, MMCs have the potential to alter offspring immune responses to antigenic challenge including malarial and Epstein-Barr virus infection. Whether maternal immune states arising from infection and immunization during pregnancy alters the nature of microchimerism and subsequent offspring immune responses is unknown. Our proposal addresses this knowledge gap. Accumulating evidence, most recently from the SARS-CoV-2 pandemic, indicate that many infectious diseases affect children differently than adults. Understanding these differences, including how maternal factors contribute to the functional plasticity of early life immune responses, will yield important insight into disease pathogenesis and inform development of new therapeutics.

PI/PD：Jain、Nitya 博士项目概要生命早期的免疫力会在一段时间内发展和成熟，使新生儿容易受到不良影响微生物遭遇。事实上，细菌感染是早产儿和足月新生儿死亡的主要原因。转移给后代的保护性母性因素是这一脆弱时期的重要防线。这种保护的一个方面来自于植入的母体微嵌合细胞（MMC），这些细胞被转移到怀孕期间的后代。在人类中，MMC 有可能改变后代的免疫反应抗原挑战，包括疟疾和 Epstein-Barr 病毒感染。母体免疫状态是否怀孕期间的感染和免疫引起的微嵌合体的性质改变，随后后代的免疫反应尚不清楚。我们的建议解决了这一知识差距。越来越多的证据（最近来自 SARS-CoV-2 大流行）表明，许多传染病对儿童的影响与成人不同。了解这些差异，包括母亲因素如何有助于早期生命免疫反应的功能可塑性，将产生对疾病的重要见解发病机制并为新疗法的开发提供信息。