Placental Immunity to LCMV

胎盘对 LCMV 的免疫

基本信息

批准号：
7776884
负责人：
ELIZABETH A. BONNEY
金额：
$ 27.56万
依托单位：
UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-05-01 至 2011-06-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7776884
关键词：
Abortion Rates Activities of Daily Living Acute Affect Alphavirus Animals Antigens Antiviral Agents Area Biological Assay Birth Blood Circulation C57BL/6 Mouse CD8B1 gene Cells Cessation of life Chickenpox Cytomegalovirus Data Development Drug effect disorder Exhibits Experimental Models Face Failure Fetus Future Generations Growth Histocytochemistry Human Immune Immune response Immunity In Situ Individual Infection Kinetics Laboratories Lead Lymphoid Tissue MHC Class I Genes Maternal-Fetal Exchange Measures Mediating Memory Modeling Molecular Mothers Mus Natural Immunity Necrosis Outcome Parvovirus Peripheral Placenta Pregnancy Prevention Reagent Research Personnel Rubella Site System Systemic infection T cell response T memory cell T-Lymphocyte Technology Testing Thrombosis Time Tissues Tropism Tumor Necrosis Factor Ligand Superfamily Member 6 Uterus Vaccines Viral Viral Load result Viral Proteins Virus Virus Diseases West Nile virus adaptive immunity base cytokine experience fetal genetic selection genetic variant in vivo malformation novel peripheral blood placental transfer pregnant programs receptor response

项目摘要

We continue to be intrigued by several aspects of viral infection of the humanplacenta, including mechanism of infection, selectivity of infection, persistence or reemergence of infection, and outcome of infection. This last aspect is a particular challenge as infection with the same virus in different individuals, independent of viral load, can be associated with no effect, or fetal loss, malformation or growth abnormalities. Based on existing data about human infection with Cytomegalovirus, Rubella, and Parvovirus we assert that placental and viral factors, as well as maternal immunity affect the overall outcome of viral infection during pregnancy. Our experimental model uses Lymphocyticchoriomeningitis virus (LCMV) infection in C57BL/6 mice. Preliminary data in this model suggests that the systemic immuneresponse to LCMV, including generation of an antigen-specific memory T-cell pool during pregnancy is not different than in a non-pregnant state. However, pregnant animals, although able to clear the virus from the systemic circulation and several tissues, were not able to clear virus from the placenta before delivery and experienced a high rate of abortion. Some fetuses, completing gestation and isolated just before birth from mothers who were infected but cleared virus, also were negative for virus. This was true despite continued infection of their placentas. Infection of the placenta with LCMV is poorly understood mechanistically. Moreover, the immuneresponse to LCMV at the maternal-fetal interface has not been well characterized with the existing technology. However, both cellular infection and immune response have been extensively studied in lymphoid tissues and peripheral blood, and these studies will guide our experimental approach. Our hypothesis is that there is special tropism forLCMV in the placenta, and that this contributes significantly to the apparent difference in placental and systemic immune responses to LCMV. This application proposes development and use of new reagents and systems and immuno-histochemistry to i) delineate the local T cell response to LCMV infection of the placenta ii) determine the cellular and molecular consequences of LCMV infection at maternal-fetal interface and iii) investigate a novelplacenta!mechanism supporting high viral load after systemic infection The results will lead to a better understanding of antigen specific T cell immunityat this site and may guide development of future treatment and vaccines against agents causing persistent infectionof the placenta.

我们继续受到人类置换病毒感染的几个方面的关注，包括机制感染，感染的选择性，持久性或感染的再生以及感染结果。这最后一个方面是一个特殊的挑战，因为在不同个体中感染了同一病毒，独立于病毒载量可能与无效，胎儿丧失，畸形或生长异常有关。基于现有有关巨细胞病毒，风疹和细小病毒感染人类感染的数据，我们断言胎盘和病毒因素以及孕产妇免疫会影响怀孕期间病毒感染的总体结果。我们的实验模型使用C57BL/6小鼠中的淋巴细胞型感染病毒（LCMV）感染。此模型中的初步数据表明，对LCMV的系统性免疫反应，包括生成怀孕期间的抗原特异性记忆T细胞池与非怀孕状态没有什么不同。然而，怀孕的动物，尽管能够从全身循环和几个组织中清除病毒，但在分娩前无法从胎盘中清除病毒，并且经历了较高的流产率。一些胎儿，完成妊娠并在出生前与被感染但清除病毒清除的母亲隔离，病毒也为阴性。尽管胎盘持续感染，但这还是事实。感染具有LCMV的胎盘的机械理解较少。此外，对LCMV的免疫响应现有技术的母亲界面尚未得到很好的特征。但是，两个细胞感染和免疫反应已在淋巴组织和外周血中进行了广泛的研究，以及这些研究将指导我们的实验方法。我们的假设是有特殊的Tropism forlcmv 在胎盘中，这对胎盘和系统性的明显差异做出了重大贡献对LCMV的免疫反应。该应用建议开发和使用新试剂和系统 i）描述了局部T细胞对胎盘II的LCMV感染的反应）确定LCMV感染在母亲界面和III上的细胞和分子后果）研究系统感染后支持高病毒负荷的新型置换机制使对抗原特异性T细胞免疫有更好的理解此站点，并可能指导开发未来的治疗和针对导致胎盘持续感染的药物的疫苗。