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

摘要 母体/胎儿界面的免疫细胞扮演着协调免疫耐受的双重角色，这是 在维持妊娠的同时，还可以预防胎盘病原体，如巨细胞病毒(CMV)。 特殊的抑制性免疫细胞，称为自然杀伤(NK)细胞，是主要的动态免疫细胞。 在整个妊娠过程中，蜕膜中充满了细胞。然而，在我们对……的作用的理解上存在很大差距。 NK细胞在保护胎儿免受免疫排斥和病原体侵袭中的作用NK细胞的作用， 包括最近发现的巨细胞病毒(CMV)特异性记忆NK细胞，在胎儿之间的相互作用 对先天性巨细胞病毒传播的耐受性和保护作用尚不明确。这项研究旨在界定 母体NK细胞群在调节胎儿耐受性和保护胎盘CMV中的作用 母体CMV慢性感染背景下的传播。我们的团队拥有独一无二的装备来剖析 在母胎界面的免疫功能在非人灵长类动物中都具有显著的专业知识 妊娠和胎盘巨细胞病毒传播的(NHP)模型以及免疫细胞的研究 人胎盘和脐带血中的母胎界面。NHP模型提供了研究 选择性采集胎儿和妊娠各阶段妊娠的免疫学和生理学 在母婴交界处获得免疫细胞，以及针对外周和 体内效应NK细胞的组织耗竭。我们假设母体NK细胞对母体和母体的 妊娠维持与早期巨细胞病毒复活的预防。理解这一点 保持免疫耐受性和预防胎盘病原体之间的交叉是至关重要的 制定以免疫为基础的策略，以减少不良妊娠造成的发病率和死亡率 结果。

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.