The obligate intracellular pathogen Coxiella burnetii is the causative agent of the zoonosis Q fever. C. burnetii infection can have severe outcomes due to the development of chronic infection. To establish and maintain an infection, C. burnetii depends on a functional type IVB secretion system (T4BSS) and, thus, on the translocation of effector proteins into the host cell. Here, we showed that the C. burnetii T4BSS effector protein CaeB targets the conserved endoplasmatic reticulum (ER) stress sensor IRE1 during ER stress in mammalian and plant cells. CaeB‐induced upregulation of IRE1 RNase activity was essential for CaeB‐mediated inhibition of ER stress‐induced cell death. Our data reveal a novel role for CaeB in ER stress signalling modulation and demonstrate that CaeB is involved in pathogenicity in vivo. Furthermore, we provide evidence that C. burnetii infection leads to modulation of the ER stress sensors IRE1 and PERK, but not ATF6 during ER stress. While the upregulation of the RNase activity of IRE1 during ER stress depends on CaeB, modulation of PERK is CaeB independent, suggesting that C. burnetii encodes several factors influencing ER stress during infection.

中文翻译：

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Coxiella burnetii 效应蛋白 CaeB 调节内质网 (ER) 应激信号，是大蜡螟有效复制所必需的

专性细胞内病原体Coxiella burnetii是人畜共患病 Q 热的病原体。由于慢性感染的发展，C.burnetii感染可能会产生严重的后果。为了建立和维持感染，C.burnetii依赖于功能型 IVB 分泌系统 (T4BSS)，因此，依赖于效应蛋白向宿主细胞的易位。在这里，我们表明C.burnetiiT4BSS 效应蛋白 CaeB 在哺乳动物和植物细胞的 ER 应激期间靶向保守的内质网 (ER) 应激传感器 IRE1。CaeB 诱导的 IRE1 RNase 活性上调对于 CaeB 介导的抑制内质网应激诱导的细胞死亡至关重要。我们的数据揭示了 CaeB 在 ER 应激信号调节中的新作用，并证明 CaeB 参与了体内致病性。此外，我们提供证据表明C.burnetii感染导致 ER 压力传感器 IRE1 和 PERK 的调节，但不会在 ER 压力期间调节 ATF6。而IRE1的RNase活性的ER应激期间上调取决于CAEB，PERK的调节是独立CAEB，表明贝氏柯克斯 编码影响感染期间内质网应激的几个因素。