The antimicrobial peptide cathelicidin protects the urinary tract against invasive bacterial infection.
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.
Chromek
Milan
M
Department of Clinical Microbiology, Microbiology and Tumorbiology Center, Karolinska University Hospital and Karolinska Institutet, SE-171 76 Stockholm, Sweden.
Slamová
Zuzana
Z
Bergman
Peter
P
Kovács
László
L
Podracká
L'udmila
L
Ehrén
Ingrid
I
Hökfelt
Tomas
T
Gudmundsson
Gudmundur H
GH
Gallo
Richard L
RL
Agerberth
Birgitta
B
Brauner
Annelie
A
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
D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins