孕期弓形虫感染致不良妊娠结局的新机制:AM/CLR/CD49a+Eome+trNK信号轴

弓形虫是一种重要生物致畸因子，其感染引起不良妊娠结局（APO）的机制复杂。CD49a+Eomes+trNK是新发现的子宫居留NK细胞，在妊娠早中期发挥类似胎盘的营养作用，其数量和功能异常与APO有关。弓形虫感染是否及如何调控这一独特细胞群尚乏研究。我们发现弓形虫感染鼠母胎界面CD49a+Eomes+trNKs数量和促进其募集的肾上腺髓质素（AM）水平明显降低，携带GRA15II遗传背景的虫株可诱导更严重的APO。据此假设：弓形虫及其效应分子GRA15II可损伤AM/CLR/CD49a+Eomes+trNKs信号轴导致APO。为此，我们拟先用Chinese1不同毒力虫株及GRA15II敲除株构建孕期感染模型，经CD49a+Eomes+trNKs过继回输，明确其在弓形虫致APO中的作用；再利用AM受体敲除鼠、体外共培养及效应分子敲除/回补，揭示弓形虫对该群细胞募集和分泌功能的关键调控分子。

T. gondii is one of the important biological teratogens. The mechanism of its infection causing adverse pregnancy outcomes (APOs) is complex. CD49a+Eomes+trNK cells are a group of newly discovered uterine resident NK cells, which play a pivotal role in providing nutrition for placenta in the early and middle stages of pregnancy. Any impairments of the quantity and function of the cells may result in APOs. However, the effect of T. gondii on these unique cells remains unknown. Our previous study indicated that the number of CD49a+Eomes+trNK cells at the maternal fetal interface of mice infected with T. gondii, and the level of adrenergic substance (AM) that promotes the cell recruitment decreased significantly. Thus we speculate that T. gondii interferes with AM/CLR/CD49a+Eomes+trNK signal axis and causes adverse pregnancy. We used strains of type Chinese1, a predomiant genotype circulating in animals and human of China, to build a model of congenital infection, through the adoptive reinfusion of CD49a+Eomes+trNK, to clarify the role of the significant immunoregulatory cells in congenital infection of T. gondii, and then used AM receptor gene knockout mice, in vitro co-culture system and knockout / supplement of the key molecules to clarify the regulatory target molecules of T. gondii on the cell recruitment and growth factor secretion function of the group. This study will help illuminate the pathogenesis of T. gondii congenital infection and lay a theoretical foundation for the formulation of novel and effective control strategies.