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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Programmed death-1 (PD-1)-deficient mice are extraordinarily sensitive to tuberculosis
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Programmed death-1 (PD-1)-deficient mice are extraordinarily sensitive to tuberculosis

机译：程序性死亡1（PD-1）缺陷小鼠对结核病极为敏感

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摘要

The programmed death-1 (PD-1) costimulatory receptor inhibits T and B cell responses and plays a crucial role in peripheral tolerance. PD-1 has recently been shown to inhibit T cell responses during chronic viral infections such as HIV. In this study, we examined the role of PD-1 in infection with Mycobacterium tuberculosis, a common co-infection with HIV. PD-1-deficient mice showed dramatically reduced survival compared with wild-type mice. The lungs of the PD-1~(-/-) mice showed uncontrolled bacterial proliferation and focal necrotic areas with predominantly neutrophilic infiltrates, but a lower number of infiltrating T and B cells. Proinflammatory cyto-kines, such as TNF-α, IL-1, and especially IL-6 and IL-17 were significantly increased in the lung and sera of infected PD-1~(-/-) mice, consistent with an aberrant inflammation. Microarray analysis of the lungs infected with M. tuberculosis showed dramatic differences between PD-1~(-/-) and control mice. Using high-stringency analysis criteria (changes of twofold or greater), 367 transcripts of genes were differentially expressed between infected PD-1~(-/-) and wild-type mice, resulting in profoundly altered inflammatory responses with implications for both innate and adaptive immunity. Overall, our studies show that the PD-1 pathway is required to control excessive inflammatory responses after M, tuberculosis infection in the lungs.
机译：程序性死亡1（PD-1）共刺激受体抑制T细胞和B细胞反应，并在外周耐受中起关键作用。最近显示，PD-1在慢性病毒感染（例如HIV）期间抑制T细胞反应。在这项研究中，我们检查了PD-1在结核分枝杆菌感染中的作用，结核分枝杆菌是HIV的常见共感染。与野生型小鼠相比，PD-1缺陷型小鼠的存活率大大降低。 PD-1〜（-/-）小鼠的肺显示出不受控制的细菌增殖和局灶性坏死区域，主要是中性粒细胞浸润，但浸润的T和B细胞数量较少。感染的PD-1〜（-/-）小鼠的肺和血清中促炎性细胞因子（如TNF-α，IL-1，尤其是IL-6和IL-17）显着增加，与异常炎症一致。对结核分枝杆菌感染的肺进行的微阵列分析显示，PD-1〜（-/-）和对照小鼠之间存在显着差异。使用高严格性分析标准（两倍或更大的变化），在受感染的PD-1〜（-/-）和野生型小鼠之间差异表达了367个基因转录本，导致炎症反应发生了深刻变化，对先天和后天都有影响。适应性免疫。总体而言，我们的研究表明，PD-1途径是控制肺结核M感染后过度炎症反应所必需的。

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    Eszter Lazar-Molnar; rnBing Chen; rnKari A. Sweeney; rnEmilie J. Wang; rnWeijun Liu; rnJuan Lin; rnSteven A. Porcelli; Steven C. Almo; rnStanley G. Nathenson; rnWilliam R. Jacobs Jr.;

  • 作者单位

    Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461;

    rnDepartment of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461 Howard Hughes Medical Institute, Albert Einstein College of Medicine, Bronx, NY 10461;

    rnDepartment of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461 Howard Hughes Medical Institute, Albert Einstein College of Medicine, Bronx, NY 10461;

    rnDepartment of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461;

    rnDepartment of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461;

    rnDepartments of Epidemiology and Population Health,Albert Einstein College of Medicine, Bronx, NY 10461;

    rnDepartment of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461;

    rnBiochemistry, Albert Einstein College of Medicine, Bronx, NY 10461 Physiology and Biophysics, Albert Einstein College of Medicine, Bronx, NY 10461;

    rnDepartment of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461 Cell Biology, Albert Einstein College of Medicine, Bronx, NY 10461;

    rnDepartment of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461 Howard Hughes Medical Institute, Albert Einstein College of Medicine, Bronx, NY 10461 Molecular Genetics, Albert Einstein College of Medicine, Bronx, NY 10461;

  • 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

    co-inhibitory; costimulatory; infection;

    机译：共同抑制共刺激感染;

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