Godaly Gabriela, Ambite Ines, Svanborg Catharina
Department of Microbiology, Immunology and Glycobiology, Institute for Laboratory Medicine, Lund University, Lund, Sweden.
Curr Opin Infect Dis. 2015 Feb;28(1):88-96. doi: 10.1097/QCO.0000000000000127.
Urinary tract infections (UTIs) are common, dangerous and interesting. Susceptible individuals experience multiple, often clustered episodes, and in a subset of patients, infections progress to acute pyelonephritis (APN), sometimes accompanied by uro-sepsis. Others develop asymptomatic bacteriuria (ABU). Here, we review the molecular basis for these differences, with the intention to distinguish exaggerated host responses that drive disease from attenuated responses that favour protection and to highlight the genetic basis for these extremes, based on knock-out mice and clinical studies.
The susceptibility to UTI is controlled by specific innate immune signalling and by promoter polymorphisms and transcription factors that modulate the expression of genes controlling these pathways. Gene deletions that disturb innate immune activation either favour asymptomatic bacteriuria or create acute morbidity and disease. Promoter polymorphisms and transcription factor variants affecting those genes are associated with susceptibility in UTI-prone patients.
It is time to start using genetics in UTI-prone patients, to improve diagnosis and to assess the risk for chronic sequels such as renal malfunction, hypertension, spontaneous abortions, dialysis and transplantation. Furthermore, the majority of UTI patients do not need follow-up, but for lack of molecular markers, they are unnecessarily investigated.
尿路感染常见、危险且有趣。易感个体常经历多次且往往呈簇状发作，部分患者感染会进展为急性肾盂肾炎（APN），有时伴有尿脓毒症。其他患者则发展为无症状菌尿（ABU）。在此，我们回顾这些差异的分子基础，旨在区分导致疾病的过度宿主反应与有利于保护的减弱反应，并基于基因敲除小鼠和临床研究突出这些极端情况的遗传基础。
对尿路感染的易感性受特定固有免疫信号传导以及启动子多态性和转录因子调控，这些转录因子可调节控制这些途径的基因表达。干扰固有免疫激活的基因缺失要么有利于无症状菌尿，要么导致急性发病和疾病。影响这些基因的启动子多态性和转录因子变体与易感患者的易感性相关。
是时候开始在易感患者中运用遗传学，以改善诊断并评估诸如肾功能不全、高血压、自然流产、透析和移植等慢性后遗症的风险了。此外，大多数尿路感染患者无需随访，但由于缺乏分子标志物，他们接受了不必要的检查。
