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AIM2 forms a complex with pyrin and ZBP1 to drive PANoptosis and host defence

机译：AIM2与吡喃和ZBP1形成复合物，以驱动胰腺和宿主防御

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摘要

Inflammasomes are important sentinels of innate immune defence, sensing pathogens and inducing cell death in infected cells'. There are several inflammasome sensorsthat each detect and respond to a specific pathogen- or damage-associated molecular pattern (PAMP or DAMP, respectively)(1). During infection, live pathogens can induce the release of multiple PAMPs and DAMPs, which can simultaneously engage multiple inflammasome sensors(2-5). Here we found that AIM2 regulatesthe innate immune sensors pyrin and ZBP1to drive inflammatory signalling and a form of inflammatory cell death known as PANoptosis, and provide host protection during infections with herpes simplex vi rusl and Francisella novicida. We also observed that AIM2, pyrin and ZBP1 were members of a large multi-protein complex along with ASC, caspase-1, caspase-8, RIPK3, RIPK1 and FADD, that drove inflammatory cell death (PANoptosis). Collectively, our findings define a previously unknown regulatory and molecular interaction between AIM2, pyrin and ZBP1that drives assembly of an AIM2-mediated multi-protein complex that we term the AIM2 PANoptosome and comprising multiple inflammasome sensors and cell death regulators. These results advance the understanding ofthe functions ofthese molecules in innate immunity and inflammatory cell death, suggesting newtherapeutic targets for AIM2-, ZBP1- and pyrin-mediated diseases.
机译：炎性炎症是先天免疫防御，感应病原体和感染细胞中的细胞死亡的重要哨兵。每个炎性传感器每次检测并响应特定的病原体或损伤相关的分子模式（PAMP或DAMP）（1）。在感染期间，活病原体可以诱导多种粘合剂和潮湿的释放，其可以同时接合多个炎性传感器（2-5）。在这里，我们发现AIM2稳定性天生的免疫传感器吡林和ZBP1驱动炎症信号传导和一种称为胰腺炎的炎症性细胞死亡，并在疱疹VI RUSL和FRANCISELLA NOVICICA感染期间提供宿主保护。我们还观察到AIM2，吡林和ZBP1是大量多蛋白复合物的成员以及ASC，Caspase-1，Caspase-8，RIPK3，RIPK1和FADD，其推动炎症性细胞死亡（胰岛凋亡）。集体，我们的发现定义了AIM2，吡林和ZBP1之间的先前未知的调节和分子相互作用，驱动AIM2介导的多蛋白复合物组合，即我们术语AIM2胰蛋白酶术语，并包含多个炎症体传感器和细胞死亡调节剂。这些结果提高了对先天免疫和炎症细胞死亡中的这些分子功能的理解，旨在为目标2-，ZBP1和吡喃和吡林介导的疾病的新靶标。

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  • 来源
    《Nature》 |2021年第7876期|415-419|共5页
  • 作者

    Lee SangJoon; Karki Rajendra; Wang Yaqiu; Nguyen Lam Nhat; Kalathur Ravi C.; Kanneganti Thirumala-Devi;

  • 作者单位

    St Jude Childrens Res Hosp Dept Immunol 332 N Lauderdale St Memphis TN 38105 USA;

    St Jude Childrens Res Hosp Dept Immunol 332 N Lauderdale St Memphis TN 38105 USA;

    St Jude Childrens Res Hosp Dept Immunol 332 N Lauderdale St Memphis TN 38105 USA;

    St Jude Childrens Res Hosp Dept Immunol 332 N Lauderdale St Memphis TN 38105 USA;

    St Jude Childrens Res Hosp Dept Struct Biol 332 N Lauderdale St Memphis TN 38105 USA;

    St Jude Childrens Res Hosp Dept Immunol 332 N Lauderdale St Memphis TN 38105 USA;

  • 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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