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

• 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
• 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

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 项目摘要 生命早期的免疫力在一段时间内发展和成熟，使新生儿容易受到不利的影响。 微生物相遇事实上，细菌感染是早产儿和足月新生儿死亡的主要原因。 在这个脆弱的时期，保护性的母体因素转移到后代是一个关键的防线。 这种保护的一个分支来自于移植的母体微嵌合细胞（MMC），其被转移到 怀孕期间的后代。在人类中，MMCs有可能改变后代的免疫反应， 抗原攻击包括疟疾和EB病毒感染。母体免疫状态是否 妊娠期间感染和免疫引起的微嵌合体改变了微嵌合体的性质， 后代的免疫反应是未知的。我们的建议解决了这一知识差距。 越来越多的证据，最近的SARS-CoV-2大流行，表明许多传染病 对儿童的影响不同于成人。了解这些差异，包括母亲因素 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 发病机制和新疗法的信息开发。