Frontiers in Cell and Developmental Biology (Feb 2021)

Campylobacter jejuni Cytolethal Distending Toxin C Exploits Lipid Rafts to Mitigate Helicobacter pylori-Induced Pathogenesis

  • Jia-Yin Yeh,
  • Hwai-Jeng Lin,
  • Hwai-Jeng Lin,
  • Chia-Jung Kuo,
  • Chia-Jung Kuo,
  • Chun-Lung Feng,
  • Chun-Lung Feng,
  • Chia-Huei Chou,
  • Chia-Huei Chou,
  • Chia-Der Lin,
  • Chia-Der Lin,
  • Hui-Yu Wu,
  • Chen-Yi Li,
  • Cheng-Hsun Chiu,
  • Cheng-Hsun Chiu,
  • Cheng-Hsun Chiu,
  • Chih-Ho Lai,
  • Chih-Ho Lai,
  • Chih-Ho Lai,
  • Chih-Ho Lai

DOI
https://doi.org/10.3389/fcell.2020.617419
Journal volume & issue
Vol. 8

Abstract

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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.

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