Are you experienced? Understanding bladder innate immunity in the context of recurrent urinary tract infection

被引:31
作者
O'Brien, Valerie P. [1 ,2 ]
Hannan, Thomas J. [3 ]
Schaeffer, Anthony J. [4 ]
Hultgren, Scott J. [1 ,2 ]
机构
[1] Washington Univ, Sch Med, Dept Mol Microbiol, St Louis, MO 63110 USA
[2] Washington Univ, Sch Med, Ctr Womens Infect Dis Res, St Louis, MO 63110 USA
[3] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA
[4] Northwestern Univ, Sch Med, Dept Urol, Chicago, IL 60611 USA
基金
美国国家卫生研究院; 美国国家科学基金会;
关键词
cystitis; mucosal immunology; urinary tract infection; uropathogenic Escherichia coli; UROPATHOGENIC ESCHERICHIA-COLI; INTRACELLULAR BACTERIAL COMMUNITIES; TRANSEPITHELIAL NEUTROPHIL MIGRATION; HOST DEFENSES; KNOCKOUT MICE; RISK-FACTORS; UROTHELIAL CELLS; ECONOMIC COSTS; YOUNG-WOMEN; MAST-CELLS;
D O I
10.1097/QCO.0000000000000130
中图分类号
R51 [传染病];
学科分类号
100401 ;
摘要
Purpose of review Recurrent urinary tract infection (rUTI) is a serious clinical problem, yet effective therapeutic options are limited, especially against multidrug-resistant uropathogens. In this review, we explore the development of a clinically relevant model of rUTI in previously infected mice and review recent developments in bladder innate immunity that may affect susceptibility to rUTI. Recent findings Chronic bladder inflammation during prolonged bacterial cystitis in mice causes bladder mucosal remodelling that sensitizes the host to rUTI. Although constitutive defenses help prevent bacterial colonization of the urinary bladder, once infection occurs, induced cytokine and myeloid cell responses predominate and the balance of immune cell defense and bladder immunopathology is critical for determining disease outcome, in both naive and experienced mice. In particular, the maintenance of the epithelial barrier appears to be essential for preventing severe infection. Summary The innate immune response plays a key role in determining susceptibility to rUTI. Future studies should be directed towards understanding how the innate immune response changes as a result of bladder mucosal remodelling in previously infected mice, and validating these findings in human clinical specimens. New therapeutics targeting the immune response should selectively target the induced innate responses that cause bladder immunopathology, while leaving protective defenses intact.
引用
收藏
页码:97 / 105
页数:9
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