Reactive oxygen species (ROS) are generated by virus-infected cells; however, the physiological importance of ROS generated under these conditions is unclear. Here we found that the inflammation and cell death induced by exposure of mice or cells to sources of ROS were not altered in the absence of canonical ROS-sensing pathways or known cell-death pathways. ROS-induced cell-death signaling involved interactions among the cellular ROS sensor and antioxidant factor KEAP1, the phosphatase PGAM5 and the proapoptotic factor AIFM1. Pgam5 ^-/- mice showed exacerbated lung inflammation and proinflammatory cytokines in an ozone-exposure model. Similarly, challenge with influenza A virus led to increased infiltration of the virus, lymphocytic bronchiolitis and reduced survival of Pgam5 ^-/- mice. This pathway, which we have called 'oxeiptosis', was a ROS-sensitive, caspase independent, non-inflammatory cell-death pathway and was important for protection against inflammation induced by ROS or ROS-generating agents such as viral pathogens.

中文翻译：

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Oxeiptosis，一种 ROS 诱导的不依赖半胱天冬酶的凋亡样细胞死亡途径。

活性氧（ROS）由病毒感染的细胞产生；然而，在这些条件下产生的 ROS 的生理重要性尚不清楚。在这里，我们发现在没有典型的 ROS 感应途径或已知的细胞死亡途径的情况下，小鼠或细胞暴露于 ROS 源诱导的炎症和细胞死亡并没有改变。ROS 诱导的细胞死亡信号涉及细胞 ROS 传感器和抗氧化因子 KEAP1、磷酸酶 PGAM5 和促凋亡因子 AIFM1 之间的相互作用。Pgam5 ^-/-小鼠在臭氧暴露模型中表现出加剧的肺部炎症和促炎细胞因子。同样，甲型流感病毒的攻击导致病毒浸润增加、淋巴细胞性细支气管炎和 Pgam5 存活率降低^-/-老鼠。我们称之为“oxeiptosis”的这一途径是一种对 ROS 敏感、不依赖于半胱天冬酶的非炎症性细胞死亡途径，对于防止由 ROS 或 ROS 产生剂（如病毒病原体）引起的炎症很重要。