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
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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.
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.
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