Bladder urothelium converts bacterial lipopolysaccharide information into neural signaling via an ATP-mediated pathway to enhance the micturition reflex for rapid defense.
Bladder urothelium converts bacterial lipopolysaccharide information into neural signaling via an ATP-mediated pathway to enhance the micturition reflex for rapid defense.
复制标题
DOI：
10.1038/s41598-020-78398-9
复制
发表时间：
2020-12-03
影响因子：
4.6
通讯作者：
Shimada S
中科院分区：
文献类型：
--
作者：
Ueda N;Kondo M;Takezawa K;Kiuchi H;Sekii Y;Inagaki Y;Soda T;Fukuhara S;Fujita K;Uemura M;Imamura R;Miyagawa Y;Nonomura N;Shimada S
当细菌进入膀胱腔时，第一阶段的主动防御机制将它们冲洗出来。虽然细菌性膀胱炎引起的尿频是一种众所周知的细菌防御反应，但其潜在机制仍不清楚。在这项研究中，使用急性细菌性膀胱炎的小鼠模型，我们证明，膀胱尿路上皮细胞通过Toll样受体4感受腔细胞外细菌脂多糖（LPS），并释放递质ATP。此外，嘌呤能P2 X2和P2 X3受体缺陷小鼠的分析表明，ATP信号在LPS诱导的L 6-S1脊髓神经元通过膀胱传入通路的激活中起着关键作用，导致排尿反射增强的快速发作。因此，我们揭示了一种新的防御机制，对细菌感染通过上皮神经的相互作用，诱导尿频细菌清除之前，由中性粒细胞的先天免疫系统。我们的研究结果表明，膀胱尿路上皮细胞作为一个化学神经换能器的重要防御作用，通过ATP介导的途径将细菌LPS信息转化为神经信号，膀胱尿路上皮细胞作为感觉受体细胞。
When bacteria enter the bladder lumen, a first-stage active defensive mechanism flushes them out. Although urinary frequency induced by bacterial cystitis is a well-known defensive response against bacteria, the underlying mechanism remains unclear. In this study, using a mouse model of acute bacterial cystitis, we demonstrate that the bladder urothelium senses luminal extracellular bacterial lipopolysaccharide (LPS) through Toll-like receptor 4 and releases the transmitter ATP. Moreover, analysis of purinergic P2X2 and P2X3 receptor-deficient mice indicated that ATP signaling plays a pivotal role in the LPS-induced activation of L6–S1 spinal neurons through the bladder afferent pathway, resulting in rapid onset of the enhanced micturition reflex. Thus, we revealed a novel defensive mechanism against bacterial infection via an epithelial-neural interaction that induces urinary frequency prior to bacterial clearance by neutrophils of the innate immune system. Our results indicate an important defense role for the bladder urothelium as a chemical-neural transducer, converting bacterial LPS information into neural signaling via an ATP-mediated pathway, with bladder urothelial cells acting as sensory receptor cells.
登录
查看更多内容
影响因子：
5.5
作者：
Ferguson, DR;Kennedy, I;Burton, TJ
通讯作者：
Burton, TJ
影响因子：
--
作者：
Cheng Y;Mansfield KJ;Allen W;Chess-Williams R;Burcher E;Moore KH
通讯作者：
Moore KH
影响因子：
2.1
作者：
Andersson, KE
通讯作者：
Andersson, KE
DOI：
10.1152/ajprenal.1998.275.2.f226
发表时间：
1998-08-01
影响因子：
4.2
作者：
Birder, LA;Apodaca, G;Kanai, AJ
通讯作者：
Kanai, AJ
DOI：
10.1073/pnas.1005333107
发表时间：
2010-11-02
影响因子：
11.1
作者：
Everaerts, Wouter;Zhen, Xiaoguang;Voets, Thomas
通讯作者：
Voets, Thomas