title: The antimicrobial peptide cathelicidin protects the urinary tract against invasive bacterial infection.
abstract: The urinary tract functions in close proximity to the outside environment, yet must remain free of microbial colonization to avoid disease. The mechanisms for establishing an antimicrobial barrier in this area are not completely understood. Here, we describe the production and function of the cathelicidin antimicrobial peptides LL-37, its precursor hCAP-18 and its ortholog CRAMP in epithelial cells of human and mouse urinary tract, respectively. Bacterial contact with epithelial cells resulted in rapid production and secretion of the respective peptides, and in humans LL-37/hCAP-18 was released into urine. Epithelium-derived cathelicidin substantially contributed to the protection of the urinary tract against infection, as shown using CRAMP-deficient and neutrophil-depleted mice. In addition, clinical E. coli strains that were more resistant to LL-37 caused more severe urinary tract infections than did susceptible strains. Thus, cathelicidin seems to be a key factor in mucosal immunity of the urinary tract.
authors.affiliation: Department of Clinical Microbiology, Microbiology and Tumorbiology Center, Karolinska University Hospital and Karolinska Institutet, SE-171 76 Stockholm, Sweden.
authors.forename: Milan
authors.initials: M
authors.lastname: Chromek
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Slamová
authors.forename: Peter
authors.initials: P
authors.lastname: Bergman
authors.forename: László
authors.initials: L
authors.lastname: Kovács
authors.forename: L'udmila
authors.initials: L
authors.lastname: Podracká
authors.forename: Ingrid
authors.initials: I
authors.lastname: Ehrén
authors.forename: Tomas
authors.initials: T
authors.lastname: Hökfelt
authors.forename: Gudmundur H
authors.initials: GH
authors.lastname: Gudmundsson
authors.forename: Richard L
authors.initials: RL
authors.lastname: Gallo
authors.forename: Birgitta
authors.initials: B
authors.lastname: Agerberth
authors.forename: Annelie
authors.initials: A
authors.lastname: Brauner
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology; D023181:Antimicrobial Cationic Peptides / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology / Q000652:urine; D002648:Child; D024881:Drug Resistance, Bacterial; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism / Q000382:microbiology; D004926:Escherichia coli / Q000187:drug effects; D004927:Escherichia coli Infections / Q000276:immunology / Q000382:microbiology* / Q000473:pathology; D006801:Humans; D018928:Immunity, Mucosal; D007672:Kidney Cortex / Q000166:cytology / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008826:Microbial Sensitivity Tests; D009504:Neutrophils / Q000378:metabolism; D014551:Urinary Tract / Q000187:drug effects / Q000382:microbiology*; D014552:Urinary Tract Infections / Q000276:immunology / Q000382:microbiology* / Q000473:pathology; D019459:Urothelium / Q000166:cytology / Q000378:metabolism / Q000382:microbiology*; D054804:Cathelicidins
chemical_list: D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins