Immunobiology of Early Pregnancy - A Model of Virus-induced Abortion

早期妊娠的免疫生物学 - 病毒引起的流产模型

• 批准号: nhmrc : 352496
• 负责人: Prof Nicholas King
• 金额: $ 30.31万
• 依托单位: The University of Sydney
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2005
• 资助国家: 澳大利亚
• 起止时间: 2005-01-01 至 2007-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/immunobiology-early-pregnancy-induced-abortion/98711
• 关键词: Immunobiology; Early; Pregnancy; Model; Virus

The lack of 'self' molecule expression on the trophoblast cells of the placenta which interface directly with the mother's circulation, as well as the local suppression of the mother's immune response at this interface, may be important factors in the successful implantation of the embryo. This immunological 'silence' allows the embryo, whose paternal genetic contribution makes it immunologically foreign to the mother, to escape the rejection reaction normally associated with foreign graft transplantation. Infection with flaviviruses increases the concentrations of cell surface self and adhesion molecules in vertebrate cells, including the trophoblast cells of the placenta. As a result, these molecules can then be recognised by the maternal immune system and the embryo targeted for destruction. We hypothesise that the induction of these molecules by this and other viruses may break the immunological silence of the early embryo and reverse the local suppression of the maternal immune response. This would result in maternal immune rejection of the embryo and abortion. This initial sensitisation of the mother by the virus might be one of the reasons that some women suffer recurrent abortions. We will use a novel viral mouse model where we implant virus-infected embryos into receptive animals to enable us to dissect out the unusual requirements for induction of maternal anti-viral immunity during pregnancy. This model was developed in our laboratory to directly test our hypotheses. It does not cause systemic illness in the mother which itself can lead to non-specific abortion. This model therefore can for the first time elucidate the specific mechanisms associated with the delicate balance between eradicating virus and maintaining pregnancy. Results from this project will inform rational design of treatment of recurrent abortions in the community.

胎盘滋养层细胞与母亲的血液循环直接相连，而胎盘滋养层细胞缺乏“自我”分子的表达，以及母亲在这一界面的免疫反应受到局部抑制，这可能是胚胎成功植入的重要因素。这种免疫“沉默”使胚胎能够避开通常与异体移植相关的排斥反应，因为胚胎的父系遗传贡献使其在免疫上对母亲来说是外来的。感染黄病毒会增加脊椎动物细胞，包括胎盘滋养层细胞中细胞表面自身和黏附分子的浓度。因此，这些分子可以被母体免疫系统识别，并以胚胎为目标进行破坏。我们假设，这种病毒和其他病毒对这些分子的诱导可能会打破早期胚胎的免疫沉默，并逆转对母体免疫反应的局部抑制。这将导致母体对胚胎的免疫排斥和流产。母亲最初对病毒的敏感可能是一些妇女遭受反复堕胎的原因之一。我们将使用一种新的病毒小鼠模型，将感染病毒的胚胎植入接受病毒的动物体内，使我们能够剖析在怀孕期间诱导母体抗病毒免疫的不寻常要求。这个模型是我们实验室开发的，用来直接检验我们的假设。它不会引起母亲的全身性疾病，而全身性疾病本身可能导致非特异性流产。因此，这个模型可以首次阐明与根除病毒和维持妊娠之间的微妙平衡有关的具体机制。该项目的结果将为合理设计社区复发性流产的治疗方案提供参考。