流产布鲁氏菌是一种兼性细胞内细菌，在巨噬细胞内复制。细胞内存活率是评价布鲁氏菌毒力的重要指标之一。铁死亡是一种由游离铁、活性氧（ROS）和有毒脂质过氧化物的积累引起的程序性细胞死亡，在癌症、心血管疾病和炎症性疾病中发挥作用。在这项研究中，我们发现布鲁氏菌粗菌株 RB51 诱导巨噬细胞铁死亡，宿主谷胱甘肽和谷胱甘肽过氧化物酶 4 (Gpx4) 水平降低，同时亚铁、脂质过氧化和 ROS 增加。抑制剂ferrostatin-1显着减少了RB51感染的巨噬细胞的铁死亡，证实了布鲁氏菌RB51感染期间发生了铁死亡。此外，我们发现RB51感染诱导的铁死亡受到P53-Slc7a11-Gpx4/GSH信号通路的调节。抑制 P53 会降低 ROS 和脂质过氧化的水平，同时恢复 Slc7a11、Gpx4 和 GSH 的水平。更重要的是，不同铁死亡抑制剂抑制铁死亡增加了布鲁氏菌RB51的细胞内存活率，表明铁死亡对布鲁氏菌细胞内存活的减弱具有作用。总的来说，我们的观察结果表明，布鲁氏菌 RB51 感染会诱导巨噬细胞铁死亡，这是由 P53-Slc7a11-Gpx4/GSH 信号通路调节的，并且对布鲁氏菌细胞内存活的减弱起作用。版权所有 © 2024。由 Elsevier B.V. 出版。

B. abortus is a facultative intracellular bacterium that replicates within macrophages. Intracellular survival is one of the important indexes to evaluate the virulence of Brucella. Ferroptosis is a type of programmed cell death induced by the accumulation of free iron, reactive oxygen species (ROS), and toxic lipid peroxides, play roles on cancers, cardiovascular diseases, and inflammatory diseases. In this study, we found that Brucella rough strain RB51 induced ferroptosis on macrophages with reduced levels of host glutathione and glutathione peroxidase 4 (Gpx4), together with increased ferrous iron, lipid peroxidation, and ROS. The inhibitor ferrostatin-1 significantly reduced the ferroptosis of RB51-infected macrophages, confirming that ferroptosis occurred during infection with Brucella RB51. Furthermore, we found that RB51 infection induced ferroptosis is regulated by P53-Slc7a11-Gpx4/GSH signal pathway. Inhibiting P53 decreased the levels of ROS and lipid peroxidation, while the levels of Slc7a11, Gpx4 and GSH were rescued. More importantly, inhibiting ferroptosis by different ferroptosis inhibitors increased the intracellular survival of Brucella RB51, indicating ferroptosis functions on the attenuation of Brucella intracellular survival. Collectively, our observations demonstrate that Brucella RB51 infection induces ferroptosis on macrophages, which is regulated by P53-Slc7a11-Gpx4/GSH signal pathway and functions on the attenuation of intracellular survival of Brucella.Copyright © 2024. Published by Elsevier B.V.