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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Hypoxia abrogates antichlamydial properties of IFN-γ in human fallopian tube cells in vitro and ex vivo
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Hypoxia abrogates antichlamydial properties of IFN-γ in human fallopian tube cells in vitro and ex vivo

机译：低氧在体外和体外消除了人输卵管细胞中IFN-γ的抗衣原体特性

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摘要

IFN-γ has an important role in the adaptive immune response against intracellular pathogens. In urogenital tract (UGT) infections with the obligate intracellular pathogen Chlamydia trachomatis, IFN-γ-mediated control of chlamydial growth implies the JAK-STAT signaling cascades and subsequent induction of the indoleamine 2,3-dioxygenase (IDO). As oxygen concentrations in the UGT are low under physiological conditions (O_2 < 5%) and further decrease during an inflammatory process, we wondered whether antibacterial properties of IFN-γ are maintained under hypoxic conditions. Using primary cells that were isolated from human fallopian tubes and an ex vivo human fallopian tube model (HFTM), we found that even high IFN-γ concentrations (200 units/ml) were not sufficient to limit growth of C. trachomatis under hypoxia. Reduced antibacterial activity of IFN-γ under hypoxia was restricted to the urogenital serovars D and L_2, but was not observed with the ocular serovar A. Impaired effectiveness of IFN-γ on chlamydial growth under hypoxia was accompanied by reduced phosphorylation of Stat-1 on Tyr701 and diminished IDO activity. This study shows that IFN-γ effector functions on intracellular C. trachomatis depend on the environmental oxygen supply, which could explain inadequate bacterial clearance and subsequent chronic infections eventually occurring in the UGT of women.
机译：IFN-γ在针对细胞内病原体的适应性免疫应答中具有重要作用。在专性细胞内病原体沙眼衣原体的泌尿生殖道（UGT）感染中，IFN-γ介导的衣原体生长的控制意味着JAK-STAT信号级联，随后诱导了吲哚胺2,3-二加氧酶（IDO）。由于UGT中的氧气浓度在生理条件下较低（O_2 <5％），并且在炎症过程中会进一步降低，因此我们想知道在低氧条件下是否能维持IFN-γ的抗菌特性。使用从人输卵管和离体人输卵管模型（HFTM）分离的原代细胞，我们发现即使高IFN-γ浓度（200单位/ ml）也不足以限制缺氧条件下沙眼衣原体的生长。缺氧条件下IFN-γ的抗菌活性降低仅限于泌尿生殖道血清D和L_2，而眼血清A则未观察到。低氧条件下IFN-γ对衣原体生长的有效性受损，同时Stat-1的磷酸化降低Tyr701和IDO活性降低。这项研究表明，IFN-γ效应子对细胞内沙眼衣原体的作用取决于环境中的氧气供应，这可以解释细菌清除不足以及最终在妇女的UGT中发生的慢性感染。

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    Anna Roth; Peter Koenig; Ger van Zandbergen; Matthias Klinger; Thomas Hellwig-Buergel; Walter Daeubener; Michael K. Bohlmann; Jan Rupp;

  • 作者单位

    Institute of Medical Microbiology and Hygiene, Center for Structural and Cell Biology in Medicine, University of Luebeck, 23538 Luebeck, Germany;

    Institute of Anatomy, Center for Structural and Cell Biology in Medicine, University of Luebeck, 23538 Luebeck, Germany;

    Institute of Medical Microbiology and Hygiene, University of Ulm, 89081 Ulm, Germany;

    Institute of Anatomy, Center for Structural and Cell Biology in Medicine, University of Luebeck, 23538 Luebeck, Germany;

    Institute of Physiology, Center for Structural and Cell Biology in Medicine, University of Luebeck, 23538 Luebeck, Germany;

    Institute for Medical Microbiology and Hospital Hygiene, Heinrich-Heine University, 40225 Duesseldorf, Germany;

    Department of Obstetrics and Gynecology, University Hospital of Schleswig-Holstein, University of Luebeck, 23538 Luebeck, Germany;

    Institute of Medical Microbiology and Hygiene, Center for Structural and Cell Biology in Medicine, University of Luebeck, 23538 Luebeck, Germany,Medical Clinic Ill/Infectious Diseases, University Hospital of Schleswig-Holstein, University of Luebeck, 23538 Luebeck, Germany;

  • 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

    Chlamydia trachomatis; hypoxia; persistence; urogenital tract infections;

    机译：沙眼衣原体缺氧坚持不懈泌尿生殖道感染;

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