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Cathelicidin protects against Helicobacter pylori colonization and the associated gastritis in mice

Gene Therapy volume 20, pages 751–760 (2013)Cite this article

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Abstract

Cathelicidin, an antimicrobial peptide of the innate immune system, has been shown to modulate microbial growth, wound healing and inflammation. However, whether cathelicidin controls Helicobacter pylori infection in vivo remains unexplored. This study sought to elucidate the role of endogenous and exogenous mouse cathelicidin (CRAMP) in the protection against H. pylori infection and the associated gastritis in mice. Results showed that genetic ablation of CRAMP in mice significantly increased the susceptibility of H. pylori colonization and the associated gastritis as compared with the wild-type control. Furthermore, replenishment with exogenous CRAMP, delivered via a bioengineered CRAMP-secreting strain of Lactococcus lactis, reduced H. pylori density in the stomach as well as the associated inflammatory cell infiltration and cytokine production. Collectively, these findings indicate that cathelicidin protects against H. pylori infection and its associated gastritis in vivo. Our study also demonstrates the feasibility of using the transformed food-grade bacteria to deliver cathelicidin, which may have potential clinical applications in the treatment of H. pylori infection in humans.

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Acknowledgements

This work was supported by the Research Fund for the Control of Infectious Diseases 08070402 from the Food and Health Bureau of Hong Kong. We also thank Ms Jean KUNG and Ms Corinna AU (School of Biomedical Sciences, The Chinese University of Hong Kong) for their technical assistance to perform immunohistochemistry and SEM; Dr Ming-hua Li (Shenzhen Nanshan Hospital) for his professional advice on the pathology of stomachs; and Mr Siu Hong Eagle CHU (Institute of Digestive Diseases, The Chinese University of Hong Kong) for his help on animal study.

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Authors and Affiliations

  1. School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China

    L Zhang, C C M Wong, Z J Li, K M Chan, S X Ren, J Shen, R L Y Chan & C H Cho

  2. Institute of Digestive Diseases, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China

    J Yu, M S M Li, A S L Cheng, J J Y Sung, W K K Wu & C H Cho

  3. Department of Microbiology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China

    T K W Ling & C C Lee

  4. Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Hong Kong, China

    K F To

  5. Division of Dermatology, University of California, San Diego, La Jolla, CA, USA

    R L Gallo

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Correspondence to W K K Wu or C H Cho.

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Zhang, L., Yu, J., Wong, C. et al. Cathelicidin protects against Helicobacter pylori colonization and the associated gastritis in mice. Gene Ther 20, 751–760 (2013). https://doi.org/10.1038/gt.2012.92

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