Newcastle University, Newcastle upon Tyne, United Kingdom.
J Urol. 2009 Jul;182(1):21-8. doi: 10.1016/j.juro.2009.02.124. Epub 2009 May 17.
The normally sterile urinary tract is constantly challenged by microbial invasion leading to a high prevalence of isolated, recurrent and catheter associated urinary tract infection. The continuous emergence of bacterial resistance following overuse of traditional antibiotics requires the urgent development of alternative treatment strategies. The involvement of innate immune mechanisms in host defense is an emerging field of microbiological research with recent work focusing on the urinary tract. We performed a comprehensive literature review to establish the current level of knowledge concerning the role of innate immunity and specifically antimicrobial peptides within the human urinary tract.
A systematic review of the literature was performed by searching PubMed from January 1988 to September 2008. Electronic searches were limited to the English language using the key words antimicrobial, peptide and urinary. Reference lists from relevant reviews were hand searched and appropriate articles were retrieved. The proceedings of conferences held in the last 2 years by the American Urological Association, European Association of Urology and British Association of Urological Surgeons were also searched.
Several defensive mechanisms have evolved in response to the threat of urinary infection, comprising physical factors and innate immune responses characterized by the expression of antimicrobial peptides. Antimicrobial peptides are small (less than 10 kDa), cationic and amphipathic peptides of variable length, sequence and structure with broad spectrum killing activity against a wide range of microorganisms including gram-positive and gram-negative bacteria. Several antimicrobial peptides have been identified in the urinary tract, and the amount and type of antimicrobial peptides expressed vary according to tissue source and disease state. These differences may reflect altered levels of innate response and, hence, susceptibility to infection. Antimicrobial peptides are already being exploited therapeutically for skin and endovascular catheter infection, and prospects for useful application in the urinary tract are emerging.
Although investigation of antimicrobial peptide function in the human urinary tract is at an early stage, it is clear that there is considerable potential for the future design of novel therapeutic strategies. More knowledge is needed concerning the pathway of involvement of antimicrobial peptides in the maintenance of urinary tract sterility and the ways in which this is altered during active infection.
正常无菌的尿路经常受到微生物入侵的挑战，导致孤立、复发性和与导管相关的尿路感染的高发。传统抗生素过度使用导致细菌耐药性的不断出现，迫切需要开发替代治疗策略。固有免疫机制在宿主防御中的作用是微生物研究的一个新兴领域，最近的工作重点是尿路。我们进行了全面的文献综述，以确定固有免疫和特别是人类尿路上皮抗菌肽的作用的现有知识水平。
通过在 1988 年 1 月至 2008 年 9 月期间在 PubMed 上进行系统的文献检索，对文献进行了回顾。电子搜索仅限于使用抗菌、肽和尿这三个关键词的英文文献。从相关综述的参考文献中进行了手工搜索，并检索了适当的文章。还搜索了过去 2 年在美国泌尿外科学会、欧洲泌尿外科学会和英国泌尿外科学会会议上发表的会议论文集。
为了应对尿路感染的威胁，已经进化出几种防御机制，包括物理因素和固有免疫反应，其特征是表达抗菌肽。抗菌肽是一种小（小于 10 kDa）、阳离子和两亲肽，其长度、序列和结构不同，对广泛的微生物具有广谱杀伤活性，包括革兰氏阳性和革兰氏阴性细菌。在尿路上皮中已经鉴定出几种抗菌肽，并且表达的抗菌肽的数量和类型根据组织来源和疾病状态而变化。这些差异可能反映了固有反应水平的改变，因此容易感染。抗菌肽已经在皮肤和血管内导管感染的治疗中得到了利用，并且在尿路上皮中的有用应用的前景正在出现。
尽管抗菌肽在人类尿路上皮中的功能研究还处于早期阶段，但很明显，未来设计新型治疗策略具有很大的潜力。需要更多地了解抗菌肽在维持尿路无菌性和在活跃感染期间这种无菌性如何改变的参与途径。
