title: Critical Role of Antimicrobial Peptide Cathelicidin for Controlling Helicobacter pylori Survival and Infection.
abstract: The antimicrobial peptide cathelicidin is critical for protection against different kinds of microbial infection. This study sought to elucidate the protective action of cathelicidin against Helicobacter pylori infection and its associated gastritis. Exogenous cathelicidin was found to inhibit H. pylori growth, destroy the bacteria biofilm, and induce morphological alterations in H. pylori membrane. Additionally, knockdown of endogenous cathelicidin in human gastric epithelial HFE-145 cells markedly increased the intracellular survival of H. pylori. Consistently, cathelicidin knockout mice exhibited stronger H. pylori colonization, higher expression of proinflammatory cytokines IL-6, IL-1β, and ICAM1, and lower expression of the anti-inflammatory cytokine IL-10 in the gastric mucosa upon H. pylori infection. In wild-type mice, H. pylori infection also stimulated gastric epithelium-derived cathelicidin production. Importantly, pretreatment with bioengineered Lactococcus lactis that actively secretes cathelicidin significantly increased mucosal cathelicidin levels and reduced H. pylori infection and the associated inflammation. Moreover, cathelicidin strengthened the barrier function of gastric mucosa by stimulating mucus synthesis. Collectively, these findings indicate that cathelicidin plays a significant role as a potential natural antibiotic for H. pylori clearance and a therapeutic agent for chronic gastritis.
authors.affiliation: Institute of Digestive Diseases and State Key Laboratory of Digestive Diseases, Li Ka Shing Institute of Health Sciences, Faculty of Medicine, Chinese University of Hong Kong, Hong Kong, China; Department of Medicine and Therapeutics, Faculty of Medicine, Chinese University of Hong Kong, Hong Kong, China; CUHK Shenzhen Research Institute, Shenzhen 518057, China; wukakei@cuhk.edu.hk linzhang@cuhk.edu.hk.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Institute of Digestive Diseases and State Key Laboratory of Digestive Diseases, Li Ka Shing Institute of Health Sciences, Faculty of Medicine, Chinese University of Hong Kong, Hong Kong, China; CUHK Shenzhen Research Institute, Shenzhen 518057, China; Department of Anesthesia and Intensive Care, Chinese University of Hong Kong, Hong Kong, China; wukakei@cuhk.edu.hk linzhang@cuhk.edu.hk.
authors.forename: William K K
authors.initials: WK
authors.lastname: Wu
authors.affiliation: Division of Dermatology, University of California, San Diego, La Jolla, CA 92093;
authors.forename: Richard L
authors.identifier: http://orcid.org/0000-0002-1401-7861
authors.initials: RL
authors.lastname: Gallo
authors.affiliation: Laboratory of Molecular Gerontology, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224;
authors.forename: Evandro F
authors.initials: EF
authors.lastname: Fang
authors.affiliation: School of Biomedical Sciences, Faculty of Medicine, Chinese University of Hong Kong, Hong Kong, China; and.
authors.forename: Wei
authors.identifier: http://orcid.org/0000-0003-0209-8032
authors.initials: W
authors.lastname: Hu
authors.affiliation: Department of Microbiology, Prince of Wales Hospital, Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Thomas K W
authors.identifier: http://orcid.org/0000-0001-7583-9167
authors.initials: TK
authors.lastname: Ling
authors.affiliation: School of Biomedical Sciences, Faculty of Medicine, Chinese University of Hong Kong, Hong Kong, China; and.
authors.forename: Jing
authors.initials: J
authors.lastname: Shen
authors.affiliation: School of Biomedical Sciences, Faculty of Medicine, Chinese University of Hong Kong, Hong Kong, China; and.
authors.forename: Ruby L Y
authors.initials: RL
authors.lastname: Chan
authors.affiliation: School of Biomedical Sciences, Faculty of Medicine, Chinese University of Hong Kong, Hong Kong, China; and.
authors.forename: Lan
authors.initials: L
authors.lastname: Lu
authors.affiliation: School of Biomedical Sciences, Faculty of Medicine, Chinese University of Hong Kong, Hong Kong, China; and.
authors.forename: Xiao M
authors.identifier: http://orcid.org/0000-0002-2334-6544
authors.initials: XM
authors.lastname: Luo
authors.affiliation: School of Biomedical Sciences, Faculty of Medicine, Chinese University of Hong Kong, Hong Kong, China; and.
authors.forename: Ming X
authors.identifier: http://orcid.org/0000-0001-5729-3850
authors.initials: MX
authors.lastname: Li
authors.affiliation: School of Biomedical Sciences, Faculty of Medicine, Chinese University of Hong Kong, Hong Kong, China; and.
authors.forename: Kam M
authors.initials: KM
authors.lastname: Chan
authors.affiliation: Institute of Digestive Diseases and State Key Laboratory of Digestive Diseases, Li Ka Shing Institute of Health Sciences, Faculty of Medicine, Chinese University of Hong Kong, Hong Kong, China; Department of Medicine and Therapeutics, Faculty of Medicine, Chinese University of Hong Kong, Hong Kong, China; CUHK Shenzhen Research Institute, Shenzhen 518057, China;
authors.forename: Jun
authors.identifier: http://orcid.org/0000-0001-5008-2153
authors.initials: J
authors.lastname: Yu
authors.affiliation: Institute of Digestive Diseases and State Key Laboratory of Digestive Diseases, Li Ka Shing Institute of Health Sciences, Faculty of Medicine, Chinese University of Hong Kong, Hong Kong, China; Department of Medicine and Therapeutics, Faculty of Medicine, Chinese University of Hong Kong, Hong Kong, China;
authors.forename: Vincent W S
authors.identifier: http://orcid.org/0000-0003-2215-9410
authors.initials: VW
authors.lastname: Wong
authors.affiliation: Institute of Digestive Diseases and State Key Laboratory of Digestive Diseases, Li Ka Shing Institute of Health Sciences, Faculty of Medicine, Chinese University of Hong Kong, Hong Kong, China; Department of Medicine and Therapeutics, Faculty of Medicine, Chinese University of Hong Kong, Hong Kong, China;
authors.forename: Siew C
authors.initials: SC
authors.lastname: Ng
authors.affiliation: Institute of Digestive Diseases and State Key Laboratory of Digestive Diseases, Li Ka Shing Institute of Health Sciences, Faculty of Medicine, Chinese University of Hong Kong, Hong Kong, China; Department of Medicine and Therapeutics, Faculty of Medicine, Chinese University of Hong Kong, Hong Kong, China; CUHK Shenzhen Research Institute, Shenzhen 518057, China;
authors.forename: Sunny H
authors.identifier: http://orcid.org/0000-0002-3354-9310
authors.initials: SH
authors.lastname: Wong
authors.affiliation: Institute of Digestive Diseases and State Key Laboratory of Digestive Diseases, Li Ka Shing Institute of Health Sciences, Faculty of Medicine, Chinese University of Hong Kong, Hong Kong, China; Department of Medicine and Therapeutics, Faculty of Medicine, Chinese University of Hong Kong, Hong Kong, China; CUHK Shenzhen Research Institute, Shenzhen 518057, China;
authors.forename: Francis K L
authors.identifier: http://orcid.org/0000-0001-7388-2436
authors.initials: FK
authors.lastname: Chan
authors.affiliation: Institute of Digestive Diseases and State Key Laboratory of Digestive Diseases, Li Ka Shing Institute of Health Sciences, Faculty of Medicine, Chinese University of Hong Kong, Hong Kong, China; Department of Medicine and Therapeutics, Faculty of Medicine, Chinese University of Hong Kong, Hong Kong, China; CUHK Shenzhen Research Institute, Shenzhen 518057, China;
authors.forename: Joseph J Y
authors.initials: JJ
authors.lastname: Sung
authors.affiliation: Department of Anesthesia and Intensive Care, Chinese University of Hong Kong, Hong Kong, China;
authors.forename: Matthew T V
authors.identifier: http://orcid.org/0000-0002-3574-7855
authors.initials: MT
authors.lastname: Chan
authors.affiliation: School of Biomedical Sciences, Faculty of Medicine, Chinese University of Hong Kong, Hong Kong, China; and.
authors.forename: Chi H
authors.initials: CH
authors.lastname: Cho
mesh_terms: D000818:Animals; D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins / Q000276:immunology*; D002460:Cell Line; D004195:Disease Models, Animal; D005455:Fluorescent Antibody Technique; D005753:Gastric Mucosa / Q000276:immunology* / Q000382:microbiology; D005756:Gastritis / Q000276:immunology*; D016481:Helicobacter Infections / Q000276:immunology*; D016480:Helicobacter pylori / Q000276:immunology; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008855:Microscopy, Electron, Scanning; D034741:RNA, Small Interfering; D060888:Real-Time Polymerase Chain Reaction; D014162:Transfection
chemical_list: D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins; D034741:RNA, Small Interfering