RAGE participates in the intracellular transport of Campylobacter jejuni cytolethal distending toxin

IF 4.5 2区 医学 Q2 IMMUNOLOGY Journal of Microbiology Immunology and Infection Pub Date : 2024-08-03 DOI:10.1016/j.jmii.2024.07.007
Yu-Fang Chang , Yi-Ping Huang , Chia-Huei Chou , Mao-Wang Ho , Hwai-Jeng Lin , Chun-Ya Chen , Hui-Yu Wu , Yi-Ru Lai , Yuan-Haw Lee , Cheng-Hsun Chiu , Chih-Ho Lai
{"title":"RAGE participates in the intracellular transport of Campylobacter jejuni cytolethal distending toxin","authors":"Yu-Fang Chang ,&nbsp;Yi-Ping Huang ,&nbsp;Chia-Huei Chou ,&nbsp;Mao-Wang Ho ,&nbsp;Hwai-Jeng Lin ,&nbsp;Chun-Ya Chen ,&nbsp;Hui-Yu Wu ,&nbsp;Yi-Ru Lai ,&nbsp;Yuan-Haw Lee ,&nbsp;Cheng-Hsun Chiu ,&nbsp;Chih-Ho Lai","doi":"10.1016/j.jmii.2024.07.007","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><p>Cytolethal distending toxin (CDT) belongs to the genotoxin family and is closely related to <em>Campylobacter jejuni</em>-associated gastroenteritis. We recently reported that CDT triggers the danger-associated molecular pattern (DAMP) signaling to exert deleterious effects on host cells. However, how CDT traffics in cells and the mechanism of CDT intoxication remain to be elucidated.</p></div><div><h3>Methods</h3><p>Recombinant CDT subunits (CdtA, CdtB, and CdtC) were purified, and their activity was characterized in gastrointestinal cells. Molecular approaches and image tracking were employed to analyze the delivery of CDT in host cells.</p></div><div><h3>Results</h3><p>In this study, we found that CDT interacts with the receptor of advanced glycation end products (RAGE) and high mobility group box 1 (HMGB1) to enter the cells. Our results further showed that CdtB transport in cells through the dynamin-dependent endocytic pathway and lysosome is involved in this process. Conversely, blockage of RAGE signaling resulted in a reduction in CDT-arrested cell cycles, indicating that RAGE is involved in CDT intracellular transport and its subsequent pathogenesis.</p></div><div><h3>Conclusion</h3><p>Our results demonstrate that RAGE is important for CDT trafficking in the cells. These findings expand our understanding of important issues related to host cell intoxication by <em>C. jejuni</em> CDT.</p></div>","PeriodicalId":56117,"journal":{"name":"Journal of Microbiology Immunology and Infection","volume":null,"pages":null},"PeriodicalIF":4.5000,"publicationDate":"2024-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S168411822400118X/pdfft?md5=a3484fdd0b8722779904c781aae8d6e9&pid=1-s2.0-S168411822400118X-main.pdf","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Microbiology Immunology and Infection","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S168411822400118X","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Background

Cytolethal distending toxin (CDT) belongs to the genotoxin family and is closely related to Campylobacter jejuni-associated gastroenteritis. We recently reported that CDT triggers the danger-associated molecular pattern (DAMP) signaling to exert deleterious effects on host cells. However, how CDT traffics in cells and the mechanism of CDT intoxication remain to be elucidated.

Methods

Recombinant CDT subunits (CdtA, CdtB, and CdtC) were purified, and their activity was characterized in gastrointestinal cells. Molecular approaches and image tracking were employed to analyze the delivery of CDT in host cells.

Results

In this study, we found that CDT interacts with the receptor of advanced glycation end products (RAGE) and high mobility group box 1 (HMGB1) to enter the cells. Our results further showed that CdtB transport in cells through the dynamin-dependent endocytic pathway and lysosome is involved in this process. Conversely, blockage of RAGE signaling resulted in a reduction in CDT-arrested cell cycles, indicating that RAGE is involved in CDT intracellular transport and its subsequent pathogenesis.

Conclusion

Our results demonstrate that RAGE is important for CDT trafficking in the cells. These findings expand our understanding of important issues related to host cell intoxication by C. jejuni CDT.

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
RAGE 参与空肠弯曲杆菌细胞致死膨胀毒素的细胞内转运。
背景:细胞致死膨胀毒素(CDT)属于基因毒素家族,与空肠弯曲菌相关性胃肠炎密切相关。我们最近报道了 CDT 触发危险相关分子模式(DAMP)信号转导,对宿主细胞产生有害影响。然而,CDT如何在细胞内迁移以及CDT中毒的机制仍有待阐明:方法:纯化重组 CDT 亚基(CdtA、CdtB 和 CdtC)并鉴定其在胃肠道细胞中的活性。我们采用分子方法和图像追踪技术分析了 CDT 在宿主细胞中的传递情况:结果:在这项研究中,我们发现 CDT 与高级糖化终产物受体(RAGE)和高迁移率基团框 1(HMGB1)相互作用,从而进入细胞。我们的研究结果进一步表明,CdtB 在细胞内的转运是通过依赖 dynamin 的内细胞途径进行的,溶酶体参与了这一过程。相反,阻断 RAGE 信号传导会导致 CDT 停滞细胞周期的减少,这表明 RAGE 参与了 CDT 的胞内转运及其随后的发病机制:我们的研究结果表明,RAGE 对 CDT 在细胞内的转运具有重要作用。结论:我们的研究结果表明,RAGE 对 CDT 在细胞内的转运具有重要作用。这些发现拓展了我们对空肠病菌 CDT 致宿主细胞中毒相关重要问题的认识。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 去求助
来源期刊
Journal of Microbiology Immunology and Infection
Journal of Microbiology Immunology and Infection IMMUNOLOGY-INFECTIOUS DISEASES
CiteScore
15.90
自引率
5.40%
发文量
159
审稿时长
67 days
期刊介绍: Journal of Microbiology Immunology and Infection is an open access journal, committed to disseminating information on the latest trends and advances in microbiology, immunology, infectious diseases and parasitology. Article types considered include perspectives, review articles, original articles, brief reports and correspondence. With the aim of promoting effective and accurate scientific information, an expert panel of referees constitutes the backbone of the peer-review process in evaluating the quality and content of manuscripts submitted for publication.
期刊最新文献
Cigarette smoke compromises macrophage innate sensing in response to pneumococcal infection. Impacts of Pta-AckA pathway on CPS biosynthesis and type 3 fimbriae expression in Klebsiella pneumoniae. Serum Mpox-specific IgG titers before and after breakthrough Mpox infection in an HIV-infected individual with viral suppression and prior 2-dose Mpox vaccination. Alternations of the gut microbiota and the Firmicutes/Bacteroidetes ratio after biologic treatment in inflammatory bowel disease. Unveiling unique effector function-related bulk antibody profiles in long-term hemodialysis patients following COVID-19 mRNA booster vaccination.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1