Upon invasive bacterial infection of colonic epithelium, host cells induce several types of cell death to eliminate pathogens. For instance, necroptosis is a RIPK‐dependent lytic cell death that serves as a backup system to fully eliminate intracellular pathogens when apoptosis is inhibited; this phenomenon has been termed “cell death crosstalk”. To maintain their replicative niche and multiply within cells, some enteric pathogens prevent epithelial cell death by delivering effectors via the type III secretion system. In this study, we found that Shigella hijacks host cell death crosstalk via a dual mechanism: inhibition of apoptosis by the OspC1 effector and inhibition of necroptosis by the OspD3 effector. Upon infection by Shigella, host cells recognize blockade of caspase‐8 apoptosis signaling by OspC1 effector as a key danger signal and trigger necroptosis as a backup form of host defense. To counteract this backup defense, Shigella delivers the OspD3 effector, a protease, to degrade RIPK1 and RIPK3, preventing necroptosis. We believe that blockade of host cell death crosstalk by Shigella is a unique intracellular survival tactic for prolonging the bacterium's replicative niche.

中文翻译：

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一种独特的细菌策略，可避免由caspase-8阻断引起的细胞死亡串扰。

在结肠上皮的侵入性细菌感染后，宿主细胞诱导几种类型的细胞死亡以消除病原体。例如，坏死病是一种依赖RIPK的裂解细胞死亡，当细胞凋亡受到抑制时，它可以作为一种备用系统来完全消除细胞内病原体。这种现象被称为“细胞死亡串扰”。为了维持其复制位并在细胞内繁殖，一些肠道病原体通过通过III型分泌系统传递效应子来防止上皮细胞死亡。在这项研究中，我们发现志贺氏菌通过双重机制劫持宿主细胞死亡串扰：通过OspC1效应子抑制凋亡和通过OspD3效应子抑制坏死病。感染志贺氏菌后，宿主细胞将OspC1效应子对caspase-8凋亡信号的阻断视为关键危险信号，并触发坏死病作为宿主防御的备用形式。为了抵消这种后备防御，志贺氏菌提供了一种蛋白酶OspD3效应物，以降解RIPK1和RIPK3，从而防止坏死。我们相信志贺氏菌对宿主细胞死亡串扰的阻止是延长细菌复制性利基的独特细胞内生存策略。