Department of Microbiology and Immunology, 5641 Medical Science Building II, 1150 West Medical Center Drive, Ann Arbor, MI 48109-0620, USA.
Infect Immun. 2010 Feb;78(2):568-85. doi: 10.1128/IAI.01000-09. Epub 2009 Nov 16.
Urinary tract infection (UTI) caused by uropathogenic Escherichia coli (UPEC) is a substantial economic and societal burden-a formidable public health issue. Symptomatic UTI causes significant discomfort in infected patients, results in lost productivity, predisposes individuals to more serious infections, and usually necessitates antibiotic therapy. There is no licensed vaccine available for prevention of UTI in humans in the United States, likely due to the challenge of targeting a relatively heterogeneous group of pathogenic strains in a unique physiological niche. Despite significant advances in the understanding of UPEC biology, mechanistic details regarding the host response to UTI and full comprehension of genetic loci that influence susceptibility require additional work. Currently, there is an appreciation for the role of classic innate immune responses-from pattern receptor recognition to recruitment of phagocytic cells-that occur during UPEC-mediated UTI. There is, however, a clear disconnect regarding how factors involved in the innate immune response to UPEC stimulate acquired immunity that facilitates enhanced clearance upon reinfection. Unraveling the molecular details of this process is vital in the development of a successful vaccine for prevention of human UTI. Here, we survey the current understanding of host responses to UPEC-mediated UTI with an eye on molecular and cellular factors whose activity may be harnessed by a vaccine that stimulates lasting and sterilizing immunity.
尿路感染（UTI）由尿路致病性大肠杆菌（UPEC）引起，给社会带来了沉重的经济和社会负担，是一个严重的公共卫生问题。有症状的 UTI 会给感染患者带来极大的不适，导致生产力下降，使个体易患更严重的感染，通常需要抗生素治疗。在美国，尚无针对 UTI 的许可疫苗，这可能是由于难以针对特定生理部位中相对异质的致病菌株进行靶向。尽管人们对 UPEC 生物学有了深入的了解，但对于宿主对 UTI 的反应机制细节以及影响易感性的遗传基因座的全面理解仍需要进一步研究。目前，人们已经认识到经典先天免疫反应的作用——从模式受体识别到吞噬细胞的募集——在 UPEC 介导的 UTI 中发生。然而，对于先天免疫反应中涉及的因素如何刺激获得性免疫，从而促进再次感染时的清除，目前还存在明显的脱节。揭示这一过程的分子细节对于开发预防人类 UTI 的成功疫苗至关重要。在这里，我们调查了宿主对 UPEC 介导的 UTI 的反应的现有认识，着眼于可能被刺激持久和杀菌免疫的疫苗利用的分子和细胞因素。
