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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Transfer of IgG in the female genital tract by MHC class I-related neonatal Fc receptor (FcRn) confers protective immunity to vaginal infection
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Transfer of IgG in the female genital tract by MHC class I-related neonatal Fc receptor (FcRn) confers protective immunity to vaginal infection

机译：MHC I类相关的新生儿Fc受体（FcRn）在女性生殖道中转移IgG，可赋予阴道感染保护性免疫力

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摘要

IgG is a major Ig subclass in mucosal secretions of the human female genital tract, where it predominates over the IgA isotype. Despite the abundance of IgG, surprisingly little is known about where and how IgG enters the lumen of the genital tract and the exact role local IgG plays in preventing sexually transmitted diseases. We demonstrate here that the neonatal Fc receptor, FcRn, is expressed in female genital tract epithelial cells of humans and mice and binds IgG in a pH-dependent manner. In vitro we show that FcRn mediates bidirectional IgG transport across polarized human endometrial HEC-1-A monolayers and primary human genital epithelial cells. Furthermore, endosomal acidification appears to be a prerequisite for FcRn-mediated IgG transcytosis; IgG transcytosis was demonstrated in vivo by translocation of systemically administered IgG into the genital lumen in WT but not FcRn-KO mice. The biological relevance of FcRn-transported IgG was demonstrated by passive immunization using herpes simplex virus-2 (HSV-2)-specific polyclonal serum, which conferred significantly higher protection against intravaginal challenge infection by the HSV-2 186 strain in WT mice than in FcRn-KO mice. These studies demonstrate that FcRn-mediated transport is a mechanism by which IgG can act locally in the female genital tract in immune surveillance and in host defense against sexually transmitted diseases.
机译：IgG是人类女性生殖道粘膜分泌物中的主要Ig亚类，在该类IgA亚型中占主导地位。尽管存在大量的IgG，但令人惊讶的是，人们对IgG在何处以及如何进入生殖道内腔以及局部IgG在预防性传播疾病中所起的确切作用知之甚少。我们在这里证明，新生儿Fc受体FcRn在人和小鼠的女性生殖道上皮细胞中表达，并以pH依赖的方式结合IgG。在体外，我们显示FcRn介导了极化的人子宫内膜HEC-1-A单层细胞和原代人生殖器上皮细胞的双向IgG转运。此外，内体酸化似乎是FcRn介导的IgG转胞吞作用的先决条件。通过全身施用的IgG易位到WT而非FcRn-KO小鼠的生殖器内腔中，体内证明了IgG的胞吞作用。通过使用单纯疱疹病毒2（HSV-2）特异性多克隆血清进行被动免疫证明了FcRn转运IgG的生物学相关性，与野生型小鼠相比，HSV-2 186菌株对阴道内挑战的感染具有更高的保护作用。 FcRn-KO小鼠。这些研究表明，FcRn介导的转运是一种机制，通过该机制，IgG可以在女性生殖道中局部发挥作用，从而进行免疫监测和宿主防御性传播疾病。

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  • 作者

    Zili Li; Senthilkumar Palaniyandi; Rongyu Zeng; Wenbin Tuo; Derry C. Roopenian; Xiaoping Zhu;

  • 作者单位

    Laboratory of Immunology, Virginia-Maryland Regional College of Veterinary Medicine, College Park, MD 20742 Maryland Pathogen Research Institute, University of Maryland, College Park, MD 20742;

    Laboratory of Immunology, Virginia-Maryland Regional College of Veterinary Medicine, College Park, MD 20742 Maryland Pathogen Research Institute, University of Maryland, College Park, MD 20742;

    Laboratory of Immunology, Virginia-Maryland Regional College of Veterinary Medicine, College Park, MD 20742 Maryland Pathogen Research Institute, University of Maryland, College Park, MD 20742;

    Animal Parasitic Diseases Laboratory, Agricultural Research Service, United States Department of Agriculture, Beltsville, MD 20705;

    The Jackson Laboratory, Bar Harbor, ME 04609;

    Laboratory of Immunology, Virginia-Maryland Regional College of Veterinary Medicine, College Park, MD 20742 Maryland Pathogen Research Institute, University of Maryland, College Park, MD 20742;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    mucosa; humoral; uterine;

    机译：黏膜体液子宫;

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