Host cellular unfolded protein response signaling regulates Campylobacter jejuni invasion.
Host cellular unfolded protein response signaling regulates Campylobacter jejuni invasion.
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DOI：
10.1371/journal.pone.0205865
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发表时间：
2018
期刊：
影响因子：
3.7
通讯作者：
Takahashi A
中科院分区：
文献类型：
--
作者：
Tentaku A;Shimohata T;Hatayama S;Kido J;Nguyen AQ;Kanda Y;Fukushima S;Uebanso T;Iwata T;Mawatari K;Harada N;Takahashi A
空肠弯曲菌是全世界人类细菌性食源性疾病的主要原因。细菌进入宿主真核细胞涉及粘附和入侵的初始步骤，这通常会激活多种细胞信号传导途径，从而诱导先天防御系统的激活，从而导致促炎细胞因子的释放并诱导细胞凋亡。最近的研究报道，未折叠蛋白反应（UPR）是一种从内质网（ER）中清除未折叠蛋白的系统，也参与激活细胞防御机制以应对细菌感染。然而，尚无研究调查 UPR 在空肠弯曲菌感染中的作用。因此，本研究的目的是通过诱导内质网应激来推断 UPR 信号在空肠弯曲菌感染过程中的作用。结果表明空肠弯曲菌感染抑制整体蛋白质翻译。此外，空肠弯曲菌感染 12 小时诱导 eIF2α 途径激活和转录因子 CHOP 表达。有趣的是，UPR相关信号因子的敲低促进了细菌的侵袭，并且用ER应激诱导剂毒胡萝卜素和衣霉素进行治疗，降低了空肠弯曲菌的侵袭能力。对 UPR 介导的空肠弯曲菌入侵抑制机制的研究表明，UPR 信号传导不会影响细菌对宿主细胞的粘附或存活。此外，肠炎沙门氏菌或 FITC-葡聚糖的摄入量不受 UPR 信号调节。这些结果表明，UPR对细胞内摄入的影响在空肠弯曲菌感染中特别明显。这些发现首次描述了 UPR 在空肠弯曲菌感染中的作用，并揭示了新的信号通路在空肠弯曲菌入侵中的参与。 UPR信号传导参与防御空肠弯曲菌入侵的早期步骤，因此为空肠弯曲菌感染的治疗提供了潜在的治疗靶点。
Campylobacter jejuni is a major cause of bacterial foodborne illness in humans worldwide. Bacterial entry into a host eukaryotic cell involves the initial steps of adherence and invasion, which generally activate several cell-signaling pathways that induce the activation of innate defense systems, which leads to the release of proinflammatory cytokines and induction of apoptosis. Recent studies have reported that the unfolded protein response (UPR), a system to clear unfolded proteins from the endoplasmic reticulum (ER), also participates in the activation of cellular defense mechanisms in response to bacterial infection. However, no study has yet investigated the role of UPR in C. jejuni infection. Hence, the aim of this study was to deduce the role of UPR signaling via induction of ER stress in the process of C. jejuni infection. The results suggest that C. jejuni infection suppresses global protein translation. Also, 12 h of C. jejuni infection induced activation of the eIF2α pathway and expression of the transcription factor CHOP. Interestingly, bacterial invasion was facilitated by knockdown of UPR-associated signaling factors and treatment with the ER stress inducers, thapsigargin and tunicamycin, decreased the invasive ability of C. jejuni. An investigation into the mechanism of UPR-mediated inhibition of C. jejuni invasion showed that UPR signaling did not affect bacterial adhesion to or survival in the host cells. Further, Salmonella Enteritidis or FITC-dextran intake were not regulated by UPR signaling. These results indicated that the effect of UPR on intracellular intake was specifically found in C. jejuni infection. These findings are the first to describe the role of UPR in C. jejuni infection and revealed the participation of a new signaling pathway in C. jejuni invasion. UPR signaling is involved in defense against the early step of C. jejuni invasion and thus presents a potential therapeutic target for the treatment of C. jejuni infection.
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影响因子：
3.7
作者：
Iwata T;Chiku K;Amano K;Kusumoto M;Ohnishi-Kameyama M;Ono H;Akiba M
通讯作者：
Akiba M
影响因子：
16
作者：
Harding, HP;Novoa, I;Ron, D
通讯作者：
Ron, D
影响因子：
64.8
作者：
Calfon, M;Zeng, HQ;Ron, D
通讯作者：
Ron, D
DOI：
10.1016/j.bbamcr.2017.05.018
发表时间：
2017-09
期刊：
Biochimica et biophysica acta. Molecular cell research
影响因子：
--
作者：
Chang CL;Chen YJ;Liou J
通讯作者：
Liou J
哺乳动物转录因子 ATF6 以跨膜蛋白的形式合成，并在内质网应激时通过蛋白水解激活
影响因子：
3.3
作者：
Haze, K;Yoshida, H;Mori, K
通讯作者：
Mori, K