Direct Detection of Tissue-Resident Bacteria and Chronic Inflammation in the Bladder Wall of Postmenopausal Women with Recurrent Urinary Tract Infection
Direct Detection of Tissue-Resident Bacteria and Chronic Inflammation in the Bladder Wall of Postmenopausal Women with Recurrent Urinary Tract Infection
复制标题
DOI：
10.1016/j.jmb.2019.04.008
复制
发表时间：
2019-10-09
影响因子：
5.6
通讯作者：
Orth, Kim
中科院分区：
文献类型：
--
作者：
De Nisco, Nicole J.;Neugent, Michael;Orth, Kim
尿路感染（UTI）是成年女性最常见的感染，并且复发率很高，尤其是绝经后女性。复发性尿路感染 (RUTI) 大大降低了生活质量，给医疗保健系统带来沉重负担，并导致抗菌药物耐药性。由于长期抗生素治疗 RUTI 在老年女性中通常无效或耐受性差，因此必须开发新的疗法。 RUTI（尤其是绝经后女性）的分子基础仍不清楚，因为在小鼠中建立 RUTI 模型很困难，而且人类数据有限。据推测，尿路上皮的侵袭和宿主炎症的诱导是细菌病原体引起 RUTI 的关键机制。为了进一步了解人类 RUTI，我们对绝经后女性的尿液和膀胱活检样本进行了系统分析，这些女性在抗生素难治性 RUTI 的高级治疗中接受膀胱镜检查并进行三角炎电灼治疗。我们提供的直接证据表明细菌存在于绝经后 RUTI 患者的膀胱壁中，并且可以从膀胱组织中分离出多种细菌种类。组织病理学评分显示 RUTI 患者活检中有明显的水肿和尿路上皮结构的改变。在大多数患者的间充质、尿路上皮和滤泡聚集体中检测到淋巴细胞，包括血浆 B 细胞，这表明在人类 RUTI 期间局部适应性免疫反应是活跃的。这些数据提供了确凿的证据，表明细菌侵入人类尿路上皮，并表明不同的细菌种类和适应性免疫反应在人类 RUTI 中发挥着重要作用。 (C) 2019 Elsevier Ltd. 保留所有权利。
Urinary tract infections (UTIs) are the most commonly reported infections in adult women and have high rates of recurrence, especially in postmenopausal women. Recurrent UTI (RUTI) greatly reduces quality of life, places a significant burden on the healthcare system, and contributes to antimicrobial resistance. Because treatment of RUTI by long-term antibiotic therapy is often ineffective or poorly tolerated in elderly women, new therapies must be developed. The molecular basis of RUTI, especially in postmenopausal women, has remained unclear because modeling RUTI in mice is difficult, and human data are limited. Invasion of the urothelium and induction of host inflammation are hypothesized to be key mechanisms by which bacterial pathogens cause RUTI. To further our understanding of RUTI in humans, we performed a systematic analysis of urine and bladder biopsy samples from postmenopausal women undergoing cystoscopy with fulguration of trigonitis in the advanced management of antibiotic-refractory RUTI. We provide direct evidence that bacteria reside in the bladder wall of postmenopausal RUTI patients and that diverse bacterial species can be isolated from the bladder tissue. Histopathological scoring revealed significant edema and alterations of urothelial architecture in RUTI patient biopsies. Lymphocytes, including plasma B-cells, were detected within the mesenchyme, urothelium, and follicular aggregates in the majority of patients, indicating that the local adaptive immune response is active during human RUTI. These data provide conclusive evidence that bacteria invade the human urothelium and suggest that diverse bacterial species and the adaptive immune response play important roles in RUTI in humans. (C) 2019 Elsevier Ltd. All rights reserved.