The Antimicrobial Peptide Cathelicidin Protects the Urinary Tract Against Invasive Bacterial Infection

Nat Med. 2006 Jun;12(6):636-41. doi: 10.1038/nm1407. Epub 2006 Jun 4.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Infective Agents / pharmacology
  • Antimicrobial Cationic Peptides / genetics
  • Antimicrobial Cationic Peptides / metabolism*
  • Antimicrobial Cationic Peptides / pharmacology
  • Antimicrobial Cationic Peptides / urine
  • Child
  • Drug Resistance, Bacterial
  • Epithelial Cells / cytology
  • Epithelial Cells / metabolism
  • Epithelial Cells / microbiology
  • Escherichia coli / drug effects
  • Escherichia coli Infections / immunology
  • Escherichia coli Infections / microbiology*
  • Escherichia coli Infections / pathology
  • Humans
  • Immunity, Mucosal
  • Kidney Cortex / cytology
  • Kidney Cortex / metabolism
  • Kidney Cortex / microbiology
  • Kidney Cortex / pathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Microbial Sensitivity Tests
  • Neutrophils / metabolism
  • Urinary Tract / drug effects
  • Urinary Tract / microbiology*
  • Urinary Tract Infections / immunology
  • Urinary Tract Infections / microbiology*
  • Urinary Tract Infections / pathology
  • Urothelium / cytology
  • Urothelium / metabolism
  • Urothelium / microbiology*

Substances

  • Anti-Infective Agents
  • Antimicrobial Cationic Peptides
  • CAP18 lipopolysaccharide-binding protein