Department of Microbiology, Immunology and Glycobiology, Institute of Laboratory Medicine, Lund University, Lund, Sweden.
Adv Exp Med Biol. 2013;764:205-10. doi: 10.1007/978-1-4614-4726-9_17.
Urinary tract infections (UTI) are common, dangerous and interesting. This review includes a general background on UTIs and molecular mechanisms of pathogenesis. In addition, we discuss UTI susceptibility and especially the effect of genetic variation on innate immunity. The symptoms of acute pyelonephritis are caused by the innate immune response and inflammation in the urinary tract decreases renal tubular function and may give rise to renal scarring, especially in childhood. The disease severity is explained by pathogens and their virulence factors triggering signaling through Toll-like receptors (TLRs), interferon regulatory factors (IRFs) and type 1 interferons, and the activation of a host response mediating disease or pathology or clearance of infection. In children with asymptomatic bacteriuria (ABU), in contrast, bacteria persist without causing symptoms or pathology. ABU strains mostly lack virulence factors, and the lack of symptoms has largely been attributed to their lack of virulence. Recently, rapid progress has been made in the understanding of host susceptibility mechanisms. For example, genetic alterations that reduce TLR4 function are associated with ABU while polymorphisms reducing IRF3 or CXCR1 expression are associated with acute pyelonephritis and an increased risk for renal scarring. Understanding bacterial virulence and host resistance promises new tools to improve the diagnostic accuracy in children with UTI. By combining information on bacterial virulence and the host response, it should be possible to start individualizing diagnosis and therapy. Finally, we propose that the prediction of future disease risk and decisions on prophylaxis and invasive diagnostic procedures might be improved by genetic analysis.
尿路感染（UTI）很常见，也很危险，很有趣。本综述包括 UTI 的一般背景和发病机制的分子机制。此外，我们还讨论了 UTI 的易感性，特别是遗传变异对固有免疫的影响。急性肾盂肾炎的症状是由固有免疫反应和尿路感染引起的炎症引起的，它会降低肾小管功能，并可能导致肾瘢痕形成，尤其是在儿童中。疾病的严重程度可以通过病原体及其毒力因子通过 Toll 样受体（TLRs）、干扰素调节因子（IRFs）和 I 型干扰素触发信号来解释，以及激活介导疾病或病理学或清除感染的宿主反应。相比之下，在无症状菌尿（ABU）的儿童中，细菌持续存在而没有引起症状或病理学。ABU 株大多缺乏毒力因子，而缺乏症状在很大程度上归因于它们缺乏毒力。最近，人们对宿主易感性机制的理解取得了快速进展。例如，降低 TLR4 功能的遗传改变与 ABU 相关，而降低 IRF3 或 CXCR1 表达的多态性与急性肾盂肾炎和肾瘢痕形成风险增加相关。了解细菌毒力和宿主抵抗力有望为改善 UTI 儿童的诊断准确性提供新工具。通过结合细菌毒力和宿主反应的信息，应该有可能开始对诊断和治疗进行个体化。最后，我们建议通过遗传分析来改进对未来疾病风险的预测以及对预防和侵袭性诊断程序的决策。
