Endoplasmic reticulum stress and unfolded protein response in infection by intracellular parasites.
Endoplasmic reticulum stress and unfolded protein response in infection by intracellular parasites.
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DOI：
10.4155/fsoa-2017-0020
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发表时间：
2017-08
影响因子：
2.5
通讯作者：
Magnani M
中科院分区：
文献类型：
--
作者：
Galluzzi L;Diotallevi A;Magnani M
内质网(ER)生理状态的扰动会触发一种称为内质网应激反应或未折叠蛋白反应(UPR)的特殊反应。在哺乳动物细胞中，UPR是由三个ER跨膜蛋白(IRE1、PERK和ATF6)介导的，它们激活三个信号级联以恢复ER稳态。近年来，UPR、炎症和微生物感觉通路之间的相互作用已被阐明。病原体感染可导致UPR激活；此外，几种病原体颠覆UPR以促进其存活和复制。虽然UPR在病毒和细菌感染中的作用已经被描述，但关于UPR在细胞内寄生虫感染中的作用还知之甚少。在这里，我们回顾了细胞内寄生虫在宿主细胞中诱导/调节UPR的最新发现。内质网(ER)在维持体内平衡和调节先天免疫反应中起着核心作用。内质网(ER)应激的扰动导致一系列被称为未折叠蛋白反应(UPR)的信号级联反应，旨在恢复细胞内环境的稳定。UPR途径与先天免疫和炎症密切相关。事实上，许多病原体(主要是病毒和细菌)已知在宿主细胞中诱导/调节UPR。由细胞内寄生虫引发的UPR研究仍然很少。它的特性有助于解释致病机制和确定新的治疗方法的开发靶点。
Perturbations of the physiological status of the endoplasmic reticulum (ER) trigger a specific response known as the ER stress response or unfolded protein response (UPR). In mammalian cells, the UPR is mediated by three ER transmembrane proteins (IRE1, PERK and ATF6) which activate three signaling cascades to restore ER homeostasis. In recent years, a cross-talk between UPR, inflammatory and microbial sensing pathways has been elucidated. Pathogen infection can lead to UPR activation; moreover, several pathogens subvert the UPR to promote their survival and replication. While the UPR in viral and bacterial infection has been characterized, little is known about the role of UPR in intracellular parasite infection. Here, we review recent findings on UPR induction/modulation by intracellular parasites in host cells. The endoplasmic reticulum (ER) has a central role in maintaining homeostasis and in the regulation of innate immune response. Perturbations in the ER (ER stress) lead to a signaling cascade termed unfolded protein response (UPR), aimed at restoring cell homeostasis. The UPR pathways are strictly connected with innate immunity and inflammation. In fact, many pathogens (mainly viruses and bacteria) are known to induce/modulate the UPR in the host cell. The UPR triggered by intracellular parasites is still poorly investigated. Its characterization could contribute to explain the mechanisms of pathogenicity and to identify targets for the development of new therapeutic approaches.