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Role of maternal-fetal interface NK cells in pregnancy maintenance and congenital CMV transmission

母胎界面 NK 细胞在妊娠维持和先天性 CMV 传播中的作用

基本信息

批准号：
10392103
负责人：
Amitinder Kaur
金额：
$ 75.43万
依托单位：
WEILL MEDICAL COLL OF CORNELL UNIV
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：
2022-03-07 至 2027-02-28
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10392103
关键词：
Affect Amniotic Fluid Animals Antibodies Blood Blood Cells CD4 Positive T Lymphocytes Cell physiology Cells Chronic Congenital Abnormality Cytomegalovirus Cytomegalovirus Infections Decidua Decidual Cell Development Endometrium Equilibrium Event Fetal Development Fetal Tissues Fetus Fracture Frequencies Gestational Age Harvest Health Human Immune Immune System Diseases Immune Tolerance Immunity Immunocompetent Immunologic Surveillance Immunologics Immunology Impairment Inflammation Inflammatory Invaded Investigation Late pregnancy Leukocytes Macaca Macaca mulatta Maternal-Fetal Exchange Mediating Memory Methods Modeling Monitor Morbidity - disease rate Natural Killer Cells Neurologic Neurologic Deficit Peripheral Physiology Placenta Play Population Pregnancy Pregnancy Complications Pregnancy Maintenance Pregnancy Outcome Pregnancy loss Premature Birth Premature Labor Prevention Regulation Rhesus Role Sampling Second Pregnancy Trimester Testing Third Pregnancy Trimester Tissues Umbilical Cord Blood adverse pregnancy outcome base congenital cytomegalovirus congenital infection design early pregnancy effective therapy embryo/fetus antigen fetal fetal immunity hearing loss risk immune function immunogenic in utero in vivo mortality nonhuman primate novel therapeutics pathogen pregnancy prevention pregnant premature prevent receptor seropositive tool transmission process trophoblast

项目摘要

Abstract Immune cells at the maternal/fetal interface play dual roles of orchestrating immune tolerance required for pregnancy maintenance, while also protecting against placental pathogens, such as cytomegalovirus (CMV). Specialized inhibitory immune cells, known as natural killer (NK) cells, are predominant and dynamic immune cells populating the decidua throughout gestation. Yet, there is a major gap in our understanding of the role of NK cells in protection of the fetus against immune rejection and pathogen invasion. The role of NK cells, including recently identified cytomegalovirus (CMV)-specific memory NK cells, in the interplay between fetal tolerance and protection against congenital CMV transmission is poorly defined. This study aims to define the role of maternal NK cell populations in regulation of fetal tolerance and protection against placental CMV transmission in the setting of chronic maternal CMV infection. Our group is uniquely equipped to dissect the immunologic functions at the maternal-fetal interface with significant expertise in both a nonhuman primate (NHP) model of pregnancy and placental CMV transmission as well as investigations of immune cells at the maternal-fetal interface in human placenta and cord blood. The NHP model affords the opportunity to study the immunology and physiology of pregnancy across the gestational stages through elective fetal harvest and access to the immune cells at the maternal-fetal interface, as well as validated strategies for peripheral and tissue depletion of effector NK cells in vivo. We hypothesize that maternal NK cells are critical to both pregnancy maintenance and prevention of CMV reactivation in early pregnancy. Understanding this intersection between maintaining immune tolerance while protecting against placental pathogens is critical to developing immune-based strategies to reduce the morbidity and mortality resulting from adverse pregnancy outcomes.

摘要