title: Antimicrobial peptides, innate immunity, and the normally sterile urinary tract.
abstract: 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 TNFalpha) 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.
authors.affiliation: Division of Surgical Immunology, Department of Surgery, Georgetown University School of Medicine, Washington, DC, USA. maz5@georgetown.edu
authors.forename: Michael
authors.initials: M
authors.lastname: Zasloff
mesh_terms: D023181:Antimicrobial Cationic Peptides / Q000502:physiology*; D006801:Humans; D007113:Immunity, Innate / Q000502:physiology*; D051197:Toll-Like Receptor 4 / Q000502:physiology*; D014551:Urinary Tract / Q000276:immunology* / Q000382:microbiology; D014552:Urinary Tract Infections / Q000209:etiology / Q000517:prevention & control*
chemical_list: D023181:Antimicrobial Cationic Peptides; D051197:Toll-Like Receptor 4