澳大利亚沃尔特和伊丽莎·霍尔医学研究所Marco J. Herold、Andreas Strasser和墨尔本大学Sammy Bedoui研究组合作发现，多种细胞死亡途径的灵活运用和互连可预防细胞内感染。 2020年7月30日，《免疫》在线发表了这一成果。

为了研究沙门氏菌感染过程中焦亡、坏死和凋亡的相对重要性，研究人员感染了缺乏caspases-1、-11、-12和-8和受体相互作用丝氨酸/苏氨酸激酶3（RIPK3）多种组合的小鼠和巨噬细胞。焦亡、caspase-8引发的凋亡或坏死的单一缺失对沙门氏菌控制的作用很小。

但是，这些细胞死亡途径的综合缺乏导致了小鼠及其巨噬细胞无法控制细菌感染，表明宿主防御可利用几种细胞死亡途径的不同组分来限制细胞内感染。灵活使用不同的细胞死亡途径涉及细胞焦亡和凋亡起始因子和效应因子之间的广泛串扰，当缺少所有已知的细胞死亡效应因子时，起始因子caspases-1和-8也可以充当执行者。这些发现揭示了一种高度协调且灵活的细胞死亡系统，该系统具有内置的故障保护过程，可以保护宿主免受细胞内感染。

附：英文原文

Title: Flexible Usage and Interconnectivity of Diverse Cell Death Pathways Protect against Intracellular Infection

Author: Marcel Doerflinger, Yexuan Deng, Paul Whitney, Ranja Salvamoser, Sven Engel, Andrew J. Kueh, Lin Tai, Annabell Bachem, Elise Gressier, Niall D. Geoghegan, Stephen Wilcox, Kelly L. Rogers, Alexandra L. Garnham, Michael A. Dengler, Stefanie M. Bader, Gregor Ebert, Jaclyn S. Pearson, Dominic De Nardo, Nancy Wang, Chenying Yang, Milton Pereira, Clare E. Bryant, Richard A. Strugnell, James E. Vince, Marc Pellegrini, Andreas Strasser, Sammy Bedoui, Marco J. Herold

Issue&Volume: 2020-07-30

Abstract: Programmed cell death contributes to host defense against pathogens. To investigate the relative importance of pyroptosis, necroptosis, and apoptosis during Salmonella infection, we infected mice and macrophages deficient for diverse combinations of caspases-1, -11, -12, and -8 and receptor interacting serine/threonine kinase 3 (RIPK3). Loss of pyroptosis, caspase-8-driven apoptosis, or necroptosis had minor impact on Salmonella control. However, combined deficiency of these cell death pathways caused loss of bacterial control in mice and their macrophages, demonstrating that host defense can employ varying components of several cell death pathways to limit intracellular infections. This flexible use of distinct cell death pathways involved extensive cross-talk between initiators and effectors of pyroptosis and apoptosis, where initiator caspases-1 and -8 also functioned as executioners when all known effectors of cell death were absent. These findings uncover a highly coordinated and flexible cell death system with in-built fail-safe processes that protect the host from intracellular infections.

DOI: 10.1016/j.immuni.2020.07.004

Source: https://www.cell.com/immunity/fulltext/S1074-7613(20)30284-3