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Bcl-2家族成员失活促进屏障上皮细胞中Gasdermin E依赖的凋亡
作者:小柯机器人 发布时间:2021/5/16 15:11:48

美国哈佛医学院Jonathan C. Kagan、Megan H. Orzalli等研究人员合作发现,病毒介导的抗凋亡Bcl-2家族成员失活促进屏障上皮细胞中Gasdermin E依赖的凋亡。2021年5月11日,国际知名学术期刊《免疫》在线发表了这一成果。

研究人员证明,在病毒感染过程中抑制蛋白质合成是一种毒力策略,并在人类角质形成细胞中引发了凋亡。研究人员确定了BCL-2家族成员MCL-1和BCL-xL是翻译关闭的传感器。病毒或化学诱导的翻译抑制作用导致MCL-1耗竭和BCL-xL失活,从而导致线粒体损伤,Gasdermin E的caspase-3依赖性切割以及白介素-1α(IL-1α)的释放。阻断该途径增强了在人类皮肤类器官模型中的病毒复制。因此,MCL-1和BCL-xL可以充当屏障上皮内的保护蛋白,并有助于抗病毒防御。

据研究人员介绍,两组先天免疫蛋白可检测病原体。模式识别受体(PRR)结合微生物产物,而保护蛋白则通过监视细胞内的稳态过程来检测毒力因子的活性。尽管PRR在许多类型的感染中的作用是众所周知的,但保护蛋白在大多数感染环境中的作用仍知之甚少。

附:英文原文

Title: Virus-mediated inactivation of anti-apoptotic Bcl-2 family members promotes Gasdermin-E-dependent pyroptosis in barrier epithelial cells

Author: Megan H. Orzalli, Aleksandra Prochera, Laurellee Payne, Avi Smith, Jonathan A. Garlick, Jonathan C. Kagan

Issue&Volume: 2021-05-11

Abstract: Two sets of innate immune proteins detect pathogens. Pattern recognition receptors(PRRs) bind microbial products, whereas guard proteins detect virulence factor activitiesby the surveillance of homeostatic processes within cells. While PRRs are well knownfor their roles in many types of infections, the role of guard proteins in most infectiouscontexts remains less understood. Here, we demonstrated that inhibition of proteinsynthesis during viral infection is sensed as a virulence strategy and initiates pyroptosisin human keratinocytes. We identified the BCL-2 family members MCL-1 and BCL-xL assensors of translation shutdown. Virus- or chemical-induced translation inhibitionresulted in MCL-1 depletion and inactivation of BCL-xL, leading to mitochondrial damage,caspase-3-dependent cleavage of gasdermin E, and release of interleukin-1α (IL-1α).Blocking this pathway enhanced virus replication in an organoid model of human skin.Thus, MCL-1 and BCL-xL can act as guard proteins within barrier epithelia and contributeto antiviral defense.

DOI: 10.1016/j.immuni.2021.04.012

Source: https://www.cell.com/immunity/fulltext/S1074-7613(21)00174-6

期刊信息

Immunity:《免疫》,创刊于1994年。隶属于细胞出版社,最新IF:21.522
官方网址:https://www.cell.com/immunity/home
投稿链接:https://www.editorialmanager.com/immunity/default.aspx