小柯机器人

AIM2与pyrin和ZBP1形成复合物，诱导PANoptosis和宿主防御，这一成果由美国圣裘德儿童研究医院Kanneganti, Thirumala-Devi小组经过不懈努力而取得。2021年9月1日，《自然》在线发表了这项成果。

在本研究中，研究人员发现AIM2调节先天免疫感受因子pyrin和ZBP1以促进炎症信号传导和诱发一种名为PANoptosis的炎症细胞死亡形式，并在单纯疱疹病毒和弗朗西斯氏菌感染时为宿主提供保护。研究人员还观察到AIM2、pyrin和ZBP1与ASC、caspase-1、caspase-8、RIPK3、RIPK1和FADD 都隶属于一个大型多蛋白复合物，它们会导致炎症细胞死亡（PANoptosis）。

总的来说，该研究结果揭示了AIM2、pyrin和ZBP1间之前未知的调控和分子相互作用，它诱导AIM2介导多蛋白复合物组装，研究人员将其称为AIM2 PANoptosome，包括多个炎症小体感受器和细胞死亡调节因子。这些结果促进了人们对这些分子在先天免疫和炎症细胞死亡中功能的理解，为AIM2-、ZBP1-和 pyrin诱导的疾病提供了新的治疗靶点。

据悉，炎症小体是先天免疫防御的重要分子，可感知病原体并在感染细胞中诱导细胞死亡。有几类炎症小体感受器，每个感受器识别和响应特定的病原体或损伤相关分子模式（分别为PAMP或DAMP）。在感染过程中，活病原体可以诱导多种PAMP和DAMP的释放，它们可以同时与多个炎症小体感受器结合。

附：英文原文

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

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

Issue&Volume: 2021-09-01

Abstract: Inflammasomes are important sentinels of innate immune defence, sensing pathogens and inducing cell death in infected cells1. There are several inflammasome sensors that 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 sensors2,3,4,5. Here we found that AIM2 regulates the innate immune sensors pyrin and ZBP1 to drive inflammatory signalling and a form of inflammatory cell death known as PANoptosis, and provide host protection during infections with herpes simplex virus 1 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 ZBP1 that 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 of the functions of these molecules in innate immunity and inflammatory cell death, suggesting new therapeutic targets for AIM2-, ZBP1- and pyrin-mediated diseases.

DOI: 10.1038/s41586-021-03875-8

Source: https://www.nature.com/articles/s41586-021-03875-8

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html