The C5a/C5aR1 Axis Contributes to the Pathogenesis of Acute Cystitis Through Enhancement of Adhesion and Colonization of Uropathogenic E. coli.
The C5a/C5aR1 Axis Contributes to the Pathogenesis of Acute Cystitis Through Enhancement of Adhesion and Colonization of Uropathogenic E. coli.
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C5a/C5aR1 轴通过增强泌尿道致病性大肠杆菌的粘附和定植，促进急性膀胱炎的发病机制
DOI：
10.3389/fcimb.2022.824505
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发表时间：
2022
影响因子：
5.7
通讯作者：
Li, Ke
中科院分区：
文献类型：
--
作者：
Wu, Kun-Yi;Cao, Bo;Wang, Chun-Xuan;Yang, Xue-Ling;Zhao, Shu-Juan;Diao, Teng-Yue;Lin, Li-Rong;Zhao, Guo-Xiu;Zhou, Wuding;Yang, Ju-Rong;Li, Ke
我们以前的工作，使用小鼠模型的肾盂肾炎表明，C5 a/C5 aR 1轴在急性肾脏感染中起致病作用。在这项研究中，我们报告，C5 a/C5 aR 1轴也发挥了致病作用，在急性膀胱感染。C5 aR 1缺陷小鼠膀胱细菌负荷减少，膀胱组织损伤减轻，这与末端α-甘露糖残基（Man）（大肠杆菌1型菌毛的潜在配体）表达减少有关。大肠杆菌）在膀胱上皮的腔表面，并减少膀胱的早期细菌定植。在体外，C5 a刺激增强甘露糖的表达，并促进细菌粘附/定植到人膀胱上皮细胞。C5 a刺激还上调ERK 1/2和NF-κB信号传导的激活以及促炎细胞因子的基因表达（即，IL 6，IL 1b，Cxcl 1，Ccl 2），其可驱动促炎反应，导致组织损伤。施用C5 aR 1拮抗剂有效地减少膀胱细菌负荷和组织损伤。因此，我们的研究结果证明了C5 a/C5 aR 1轴在膀胱感染中的先前未知的致病作用，并表明C5 a/C5 aR 1轴介导的Man表达上调，细菌粘附/定植的增强和过度的炎症反应有助于急性膀胱感染。这些发现提高了我们对膀胱感染的发病机制的理解，并对UTI的治疗具有指导意义。
Our previous work using a murine model of pyelonephritis demonstrated that the C5a/C5aR1 axis plays a pathogenic role in acute kidney infection. In this study, we report that the C5a/C5aR1 axis also plays a pathogenic role in acute bladder infection. C5aR1-deficient mice had reduced bladder bacterial load and attenuated bladder tissue injury, which is associated with reduced expression of terminal α-mannosyl residues (Man) (a potential ligand for type 1 fimbriae of E. coli) at the luminal surface of the bladder epithelium and reduced early bacterial colonization of the bladder. In vitro, C5a stimulation enhanced mannose expression in and facilitated bacterial adhesion/colonization to human bladder epithelial cells. C5a stimulation also upregulated the activation of ERK1/2 and NF-κB signaling and gene expression of proinflammatory cytokines (i.e., Il6, Il1b, Cxcl1, Ccl2) in the epithelial cells, which could drive pro-inflammatory responses leading to tissue injury. Administration of the C5aR1 antagonist effectively reduced bladder bacterial load and tissue injury. Thus, our findings demonstrate a previously unknown pathogenic role for the C5a/C5aR1 axis in bladder infection and suggest that the C5a/C5aR1 axis-mediated upregulation of Man expression, enhancement of bacterial adhesion/colonization, and excessive inflammatory responses contribute to acute bladder infection. These findings improve our understanding of the pathogenesis of bladder infection with therapeutic implications for UTI.
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影响因子：
4.8
作者：
Bosmann, Markus;Patel, Vinay R.;Ward, Peter A.
通讯作者：
Ward, Peter A.
DOI：
10.1038/s41579-020-0324-0
发表时间：
2020-04
期刊：
Nature reviews. Microbiology
影响因子：
--
作者：
Klein RD;Hultgren SJ
通讯作者：
Hultgren SJ
影响因子：
19.6
作者：
Choudhry N;Li K;Zhang T;Wu KY;Song Y;Farrar CA;Wang N;Liu CF;Peng Q;Wu W;Sacks SH;Zhou W
通讯作者：
Zhou W
影响因子：
11.5
作者：
Lee, Arnold
通讯作者：
Lee, Arnold
影响因子：
6.7
作者：
Diabate M;Munro P;Garcia E;Jacquel A;Michel G;Obba S;Goncalves D;Luci C;Marchetti S;Demon D;Degos C;Bechah Y;Mege JL;Lamkanfi M;Auberger P;Gorvel JP;Stuart LM;Landraud L;Lemichez E;Boyer L
通讯作者：
Boyer L