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Published ahead of print on October 17, 2007
J Am Soc Nephrol 18: 2810-2816, 2007
© 2007 American Society of Nephrology
doi: 10.1681/ASN.2007050611
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Brief Review

Antimicrobial Peptides, Innate Immunity, and the Normally Sterile Urinary Tract

Michael Zasloff

Division of Surgical Immunology, Departments of Surgery and Pediatrics, Georgetown University School of Medicine, Washington, DC

Correspondence: Dr. Michael Zasloff, Department of Surgery and Pediatrics, Division of Surgical Immunology, Georgetown University School of Medicine, Washington DC. Phone: 202-687-5707; Fax: 202-687-0992; E-mail: maz5{at}georgetown.edu

Considering the anatomical location of the urethral meatus, it is surprising that urine is normally sterile. The defensive properties of uroepithelia help maintain this sterility as strategically necessary for long-term survival. Epithelia lining the urinary tract prevent adhesion of bacteria by release of Tamm-Horsfall protein, lactoferrin, lipocalin, and constitutive and inducible bactericidal antimicrobial peptides such as {alpha}- and beta-defensins and cathelicidin. Microbes that overwhelm these early defenses contact uroepithelia and activate an innate immune response through Toll-like receptor 4. With persistence of increasing numbers of microbes, chemokines (IL-8) and cytokines (IL-1 and TNF{alpha}) attract and activate large numbers of neutrophils and macrophages that damage tubulointerstitial parenchyma. The risk of serious infection in humans seems quite variable. Cathelicidin, for example, is a vitamin D–dependent gene, and vitamin D stores may influence susceptibility to urinary tract infection in selected individuals. As more knowledge accrues, vitamin D supplementation may someday be useful as adjuvant therapy in this setting.






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