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Article
Nature Medicine 12, 636 - 641 (2006)
Published online: 4 June 2006 | doi:10.1038/nm1407
The antimicrobial peptide cathelicidin protects the urinary tract against invasive bacterial infection
Milan Chromek1, Zuzana Slamová1, Peter Bergman2, László Kovács3, L'udmila Podracká4, Ingrid Ehrén5, Tomas Hökfelt6, Gudmundur H Gudmundsson7, Richard L Gallo8, Birgitta Agerberth2 & Annelie Brauner1
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.
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