TY - JOUR
T1 - Campylobacter jejuni Cytolethal Distending Toxin C Exploits Lipid Rafts to Mitigate Helicobacter pylori-Induced Pathogenesis
AU - Yeh, Jia Yin
AU - Lin, Hwai Jeng
AU - Kuo, Chia Jung
AU - Feng, Chun Lung
AU - Chou, Chia Huei
AU - Lin, Chia Der
AU - Wu, Hui Yu
AU - Li, Chen Yi
AU - Chiu, Cheng Hsun
AU - Lai, Chih Ho
N1 - Funding Information:
This work was funded by the Ministry of Science and Technology (109-2320-B-182-025-MY3 and 109-2320-B-182-029-MY3), Chang Gung Memorial Hospital at Linkou (CMRPG3K0691, CMRPD1I0061-3, CMRPD1J0021-3, CMRPD1K0361, and BMRPE90), China Medical University and Hospital (CMU103-BC-2 and DMR-104-026), and Tomorrow Medical Foundation.
Funding Information:
The authors would like to thank the editor and reviewers for the editorial assistance and their valuable comments. The authors sincerely appreciate the assistance for confocal microscope analysis (Microscopy Center, Chang Gung University, Taoyuan, Taiwan). Funding. This work was funded by the Ministry of Science and Technology (109-2320-B-182-025-MY3 and 109-2320-B-182-029-MY3), Chang Gung Memorial Hospital at Linkou (CMRPG3K0691, CMRPD1I0061-3, CMRPD1J0021-3, CMRPD1K0361, and BMRPE90), China Medical University and Hospital (CMU103-BC-2 and DMR-104-026), and Tomorrow Medical Foundation.
Publisher Copyright:
© Copyright © 2021 Yeh, Lin, Kuo, Feng, Chou, Lin, Wu, Li, Chiu and Lai.
PY - 2021/2/23
Y1 - 2021/2/23
N2 - Helicobacter pylori infection is associated with several gastrointestinal diseases, including gastritis, peptic ulcer, and gastrointestinal adenocarcinoma. Two major cytotoxins, vacuolating cytotoxin A (VacA) and cytotoxin-associated gene A (CagA), interact closely with lipid rafts, contributing to H. pylori-associated disease progression. The Campylobacter jejuni cytolethal distending toxin consists of three subunits: CdtA, CdtB, and CdtC. Among them, CdtA and CdtC bind to membrane lipid rafts, which is crucial for CdtB entry into cells. In this study, we employed recombinant CdtC (rCdtC) to antagonize the functions of H. pylori cytotoxin in cells. Our results showed that rCdtC alleviates cell vacuolation induced by H. pylori VacA. Furthermore, rCdtC reduces H. pylori CagA translocation, which decreases nuclear factor kappa-B activation and interleukin-8 production, resulting in the mitigation of gastric epithelial cell inflammation. These results reveal that CdtC hijacks cholesterol to compete for H. pylori cytotoxin actions via lipid rafts, ameliorating H. pylori-induced pathogenesis.
AB - Helicobacter pylori infection is associated with several gastrointestinal diseases, including gastritis, peptic ulcer, and gastrointestinal adenocarcinoma. Two major cytotoxins, vacuolating cytotoxin A (VacA) and cytotoxin-associated gene A (CagA), interact closely with lipid rafts, contributing to H. pylori-associated disease progression. The Campylobacter jejuni cytolethal distending toxin consists of three subunits: CdtA, CdtB, and CdtC. Among them, CdtA and CdtC bind to membrane lipid rafts, which is crucial for CdtB entry into cells. In this study, we employed recombinant CdtC (rCdtC) to antagonize the functions of H. pylori cytotoxin in cells. Our results showed that rCdtC alleviates cell vacuolation induced by H. pylori VacA. Furthermore, rCdtC reduces H. pylori CagA translocation, which decreases nuclear factor kappa-B activation and interleukin-8 production, resulting in the mitigation of gastric epithelial cell inflammation. These results reveal that CdtC hijacks cholesterol to compete for H. pylori cytotoxin actions via lipid rafts, ameliorating H. pylori-induced pathogenesis.
KW - cytolethal distending toxin
KW - cytotoxin-associated gene A
KW - Helicobacter pylori
KW - lipid rafts
KW - vacuolating cytotoxin A
UR - http://www.scopus.com/inward/record.url?scp=85102349747&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85102349747&partnerID=8YFLogxK
U2 - 10.3389/fcell.2020.617419
DO - 10.3389/fcell.2020.617419
M3 - Article
AN - SCOPUS:85102349747
SN - 2296-634X
VL - 8
JO - Frontiers in Cell and Developmental Biology
JF - Frontiers in Cell and Developmental Biology
M1 - 617419
ER -