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Galactosaminogalactan activates the inflammasome to provide host protection

机译：半乳糖酰氨基酰氯酰胺激活炎性炎症以提供主机保护

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摘要

Inflammasomes are important sentinels of innate immune defence that are activated in response to diverse stimuli, including pathogen-associated molecular patterns (PAMPs)~(1). Activation of the inflammasome provides host defence against aspergillosis~(2,3), which is a major health concern for patients who are immunocompromised. However, the Aspergillus fumigatus PAMPs that are responsible for inflammasome activation are not known. Here we show that the polysaccharide galactosaminogalactan (GAG) of A. fumigatus is a PAMP that activates the NLRP3 inflammasome. The binding of GAG to ribosomal proteins inhibited cellular translation machinery, and thus activated the NLRP3 inflammasome. The galactosamine moiety bound to ribosomal proteins and blocked cellular translation, which triggered activation of the NLRP3 inflammasome. In mice, a GAG-deficient Aspergillus mutant (Δgt4c) did not elicit protective activation of the inflammasome, and this strain exhibited enhanced virulence. Moreover, administration of GAG protected mice from colitis induced by dextran sulfate sodium in an inflammasome-dependent manner. Thus, ribosomes connect the sensing of this fungal PAMP to the activation of an innate immune response.
机译：炎症是响应于多种刺激而被激活的先天免疫防御的重要哨兵，包括病原体相关的分子模式（PAMPS）〜（1）。激活炎性体为胰岛病〜（2,3）提供宿主防御，这对于免疫造成的患者来说是一个主要的健康问题。然而，不知道负责炎症组织活化的曲霉菌菌斑纸质是不知道的。在这里，我们表明A. fumigatus的多糖半酰胺氨基酰胺（Gag）是激活NLRP3炎性的泵。 GAG对核糖体蛋白的结合抑制了细胞翻译机制，从而活化了NLRP3炎症。半乳糖胺部分与核糖体蛋白结合并封闭的细胞翻译，引发了NLRP3炎症的活化。在小鼠中，缺血性瓣膜突变体（ΔGt4c）没有引发炎症的保护活化，并且该菌株表现出增强的毒力。此外，从氨基硫酸氨酸硫酸钠诱导的结肠炎中施用GAG保护小鼠以炎症组依赖性方式。因此，核糖体将该真菌PAMP的感测到激活先天免疫应答。

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  • 来源
    《Nature》 |2020年第7839期|688-692|共5页
  • 作者

    Benoit Briard; Thierry Fontaine; Parimal Samir; David E Place; Laetitia Muszkieta; R K Subbarao Malireddi; Rajendra Karki; Shelbi Christgen; Perrine Bomme; Peter Vogel; Rémi Beau; Emilia Mellado; Oumaima Ibrahim-Granet; Bernard Henrissat; Ravi C Kalathur; Cam Robinson; Jean-Paul Latgé; Thirumala-Devi Kanneganti;

  • 作者单位

    Department of Immunology St Jude Children's Research Hospital;

    Unité des Aspergillus Institut Pasteur;

    Department of Immunology St Jude Children's Research Hospital;

    Department of Immunology St Jude Children's Research Hospital;

    Unité des Aspergillus Institut Pasteur;

    Department of Immunology St Jude Children's Research Hospital;

    Department of Immunology St Jude Children's Research Hospital;

    Department of Immunology St Jude Children's Research Hospital;

    Ultrastructural Bio Imaging Unit C2RT Institut Pasteur;

    Animal Resources Center and the Veterinary Pathology Core St Jude Children's Research Hospital;

    Unité des Aspergillus Institut Pasteur;

    Mycology Reference Laboratory Centro Nacional de Microbiologia Instituto de Salud Carlos III;

    Unité des Cytokines et Inflammation Institut Pasteur;

    AFMB|Department of Biological Sciences King Abdulaziz University;

    Department of Structural Biology St Jude Children's Research Hospital;

    Cell and Tissue Imaging Center St Jude Children's Research Hospital;

    Unité des Aspergillus Institut Pasteur|Institute of Molecular Biology and Biotechnology Foundation for Research and Technology;

    Department of Immunology St Jude Children's Research Hospital;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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