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 ␣-and ␤-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␣) 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.

Quantitative body fluid proteomics in medicine — A focus on minimal invasiveness

“…From an analytical point of view, this can also mean that utilizing mass spectrometers with high resolution mass analyzers or extensive sample fractionation, enrichment or depletion and identifying more than 100 proteins can reveal the proteome masked by the highly abundant proteins. The urine is unique in a sense that its distinct anatomical and physiological properties imply the presence of a different chemical barrier as compared to that of other body fluids [180]. The number of AMPs among the identified urine biomarkers is high but fall far less than those of other body fluids (Table 8).…”

Studies of Innate Immunity Parameters (Tlr2, Tlr4 and Hbd1) of Uretheral Mucous Epithelium in Chronic Bacterial Cystitis

“…Последние ис-следования демонстрируют, что экспрессия ге-нов противомикробных пептидов (ПМП) может быть индуцирована рядом факторов. ПМП мо-гут экспрессироваться как конститутивно, так и индуцировано, под воздействием цитокинов, вырабатывающихся моноцитами, привлеченны-ми в воспалительный очаг [15]. В работах других исследователей было показано, что в норме экс-прессия мРНК гена DEFB1 на высоком уровне выявлена в дистальных нефронах, собиратель-ной системе почек, а также в дистальном отделе уретры [4,13], что свидетельствует о важной роли данного пептида в поддержании здорового состо-яния слизистой оболочки мочевыводящих путей.…”

Innate Immune Response to Urinary Tract Infections Involving Escherichia coli

“…These AMPs, such as uromodulin, defensins, cathelicidin (LL-37), lactoferrin, hepcidin, and ribonucleases 6 and 7, are the immune system's front line attempt to keep the bacteria from being able to bind to the cells. The epithelial cells will rapidly secret AMPs when the presence of bacteria are sensed [8,9]. Many AMPs have bacteriocidal activity that is due to their distinct structure and charge which result in bacterial cell membrane disruption [10].…”

“…The β-defensins are expressed constitutively in epithelial cells. Human β-defensin-1 (HBD-1) has been found to be widely distributed in areas of the body with mucosal epithelium; and for the urinary tract more specifically, in the collecting ducts, distal tubules, and loops of Henle, where they may inhibit attachment of bacteria to the epithelial cells [8]. HBD-1 may also act as a chemoattractant for some T lymphocytes and immature dendritic cells (interact with CCR6 receptor) [8,9,15].…”

“…This affects recruitment of phagocytes, monocytes, immature dendritic cells, and T cells (interacts with fMLPreceptors). In addition, cathelicidin is responsible for release of proinflammatory molecules such as histamine and prostaglandins by degranulation of mast cells [8,9,15].…”