The antimicrobial peptide cathelicidin protects the urinary tract against invasive bacterial infection

Milan Chromek; Zuzana Slamová; Peter Bergman; László Kovács; L'udmila Podracká; Ingrid Ehrén; Tomas Hökfelt; Gudmundur H. Gudmundsson; Richard L. Gallo; Birgitta Agerberth; Annelie Brauner

doi:10.1038/nm1407

The antimicrobial peptide cathelicidin protects the urinary tract against invasive bacterial infection

Milan Chromek, Zuzana Slamová, Peter Bergman, László Kovács, L'udmila Podracká, Ingrid Ehrén, Tomas Hökfelt, Gudmundur H. Gudmundsson, Richard L. Gallo, Birgitta Agerberth, Annelie Brauner

Faculty of Life and Environmental Sciences

University of Iceland

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Pages (from-to)	636-641
Number of pages	6
Journal	Nature Medicine
Volume	12
Issue number	6
DOIs	https://doi.org/10.1038/nm1407
Publication status	Published - Jun 2006

Bibliographical note

Funding Information: We thank Z. Fehervízyová and T. Baltesová for help collecting urine samples, M. Lindh for technical assistance and G. Kronvall for help with single-strain regression analysis. This work was supported by ALF Project Funding, The Swedish Society of Medicine, The Swedish Association of Kidney Patients, funds from the Karolinska Institute, Magn. Bergvalls Foundation, Capio Foundation, The Swedish Research Council (04X-2887, 06X-11217), The Swedish Foundation for International Cooperation in Research and Higher Education (STINT), and the Knut and Alice Wallenberg Foundation.

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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.",

author = "Milan Chromek and Zuzana Slamov{\'a} and Peter Bergman and L{\'a}szl{\'o} Kov{\'a}cs and L'udmila Podrack{\'a} and Ingrid Ehr{\'e}n and Tomas H{\"o}kfelt and Gudmundsson, \{Gudmundur H.\} and Gallo, \{Richard L.\} and Birgitta Agerberth and Annelie Brauner",

note = "Funding Information: We thank Z. Feherv{\'i}zyov{\'a} and T. Baltesov{\'a} for help collecting urine samples, M. Lindh for technical assistance and G. Kronvall for help with single-strain regression analysis. This work was supported by ALF Project Funding, The Swedish Society of Medicine, The Swedish Association of Kidney Patients, funds from the Karolinska Institute, Magn. Bergvalls Foundation, Capio Foundation, The Swedish Research Council (04X-2887, 06X-11217), The Swedish Foundation for International Cooperation in Research and Higher Education (STINT), and the Knut and Alice Wallenberg Foundation.",

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AU - Chromek, Milan

AU - Slamová, Zuzana

AU - Bergman, Peter

AU - Kovács, László

AU - Podracká, L'udmila

AU - Ehrén, Ingrid

AU - Hökfelt, Tomas

AU - Gudmundsson, Gudmundur H.

AU - Gallo, Richard L.

AU - Agerberth, Birgitta

AU - Brauner, Annelie

N1 - Funding Information: We thank Z. Fehervízyová and T. Baltesová for help collecting urine samples, M. Lindh for technical assistance and G. Kronvall for help with single-strain regression analysis. This work was supported by ALF Project Funding, The Swedish Society of Medicine, The Swedish Association of Kidney Patients, funds from the Karolinska Institute, Magn. Bergvalls Foundation, Capio Foundation, The Swedish Research Council (04X-2887, 06X-11217), The Swedish Foundation for International Cooperation in Research and Higher Education (STINT), and the Knut and Alice Wallenberg Foundation.

PY - 2006/6

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N2 - 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.

AB - 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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The antimicrobial peptide cathelicidin protects the urinary tract against invasive bacterial infection

Abstract

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