Antimicrobial peptides, innate immunity, and the normally sterile urinary tract.
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.
Zasloff
Michael
M
Division of Surgical Immunology, Department of Surgery, Georgetown University School of Medicine, Washington, DC, USA. maz5@georgetown.edu
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*
D023181:Antimicrobial Cationic Peptides; D051197:Toll-Like Receptor 4