Urinary tract infections (UTIs) typically evoke prompt and vigorous innate bladder immune responses, including extensive exfoliation of the epithelium. To explain the basis for the extraordinarily high recurrence rates of UTIs, we examined adaptive immune responses in mouse bladders. We found that, following each bladder infection, a highly T helper type 2 (TH2)-skewed immune response directed at bladder re-epithelialization is observed, with limited capacity to clear infection. This response is initiated by a distinct subset of CD301b+OX40L+ dendritic cells, which migrate into the bladder epithelium after infection before trafficking to lymph nodes to preferentially activate TH2 cells. The bladder epithelial repair response is cumulative and aberrant as, after multiple infections, the epithelium was markedly thickened and bladder capacity was reduced relative to controls. Thus, recurrence of UTIs and associated bladder dysfunction are the outcome of the preferential focus of the adaptive immune response on epithelial repair at the expense of bacterial clearance.

中文翻译：

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TH2 膀胱对感染的高度极化反应促进上皮修复，但代价是防止新的感染。


尿路感染（UTI）通常会引起迅速而强烈的膀胱先天免疫反应，包括上皮的广泛脱落。为了解释尿路感染复发率极高的原因，我们检查了小鼠膀胱的适应性免疫反应。我们发现，每次膀胱感染后，都会观察到针对膀胱再上皮化的高度 T 辅助细胞 2 型 (TH2) 倾斜的免疫反应，但清除感染的能力有限。这种反应是由 CD301b+OX40L+ 树突状细胞的独特子集启动的，这些细胞在感染后迁移到膀胱上皮，然后运输到淋巴结以优先激活 TH2 细胞。膀胱上皮修复反应是累积的和异常的，因为在多次感染后，上皮明显增厚并且膀胱容量相对于对照减少。因此，尿路感染的复发和相关的膀胱功能障碍是适应性免疫反应优先关注上皮修复而牺牲细菌清除的结果。