Activation of the NLRP3 Inflammasome Pathway by Uropathogenic Escherichia coli Is Virulence Factor-Dependent and Influences Colonization of Bladder Epithelial Cells.
Activation of the NLRP3 Inflammasome Pathway by Uropathogenic Escherichia coli Is Virulence Factor-Dependent and Influences Colonization of Bladder Epithelial Cells.
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DOI：
10.3389/fcimb.2018.00081
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发表时间：
2018
影响因子：
5.7
通讯作者：
Persson K
中科院分区：
文献类型：
--
作者：
Demirel I;Persson A;Brauner A;Särndahl E;Kruse R;Persson K
NLRP3炎性体和IL-1β释放最近被认为对尿路感染（UTI）的进展很重要。然而，关于UPEC与NLRP3炎性体的相互作用仍有很多未知。本研究的目的是阐明尿路致病性大肠杆菌（UPEC）使用哪些毒力因子来调节NLRP3炎性小体激活和随后的IL-1β释放，以及NLRP3在UPEC在膀胱上皮细胞定植中的作用。用UPEC分离株和非致病性MG1655菌株刺激膀胱上皮细胞系5637、CRISPR/Cas9生成的NLRP3、caspase-1和中胰蛋白酶缺陷细胞系以及转化的原代膀胱上皮细胞（HBLAK）。我们发现，UPEC菌株CFT073，而不是MG1655，诱导膀胱上皮细胞caspase-1活性和IL-1β释放增加。结果表明，这种增加是由α-溶血素激活NLRP3炎性体介导的，其方式不依赖于NF-κ b。α-溶血素对IL-1β释放的影响呈双相性，先抑制后诱导。此外，CFT073的锁相1型纤维ON变体抑制caspase-1的激活和IL-1β的释放。此外，与野生型细胞相比，CFT073粘附和侵袭NLRP3缺陷细胞的能力显著降低。nlrp3缺陷细胞的定植减少依赖于1型菌毛。综上所述，我们发现NLRP3炎性小体对1型纤维依赖的膀胱上皮细胞定植很重要，并且1型纤维和α-溶血素都可以调节NLRP3炎性小体的活性。
The NLRP3 inflammasome and IL-1β release have recently been suggested to be important for the progression of urinary tract infection (UTI). However, much is still unknown regarding the interaction of UPEC and the NLRP3 inflammasome. The purpose of this study was to elucidate what virulence factors uropathogenic Escherichia coli (UPEC) use to modulate NLRP3 inflammasome activation and subsequent IL-1β release and the role of NLRP3 for UPEC colonization of bladder epithelial cells. The bladder epithelial cell line 5637, CRISPR/Cas9 generated NLRP3, caspase-1 and mesotrypsin deficient cell lines and transformed primary bladder epithelial cells (HBLAK) were stimulated with UPEC isolates and the non-pathogenic MG1655 strain. We found that the UPEC strain CFT073, but not MG1655, induced an increased caspase-1 activity and IL-1β release from bladder epithelial cells. The increase was shown to be mediated by α-hemolysin activation of the NLRP3 inflammasome in an NF-κB-independent manner. The effect of α-hemolysin on IL-1β release was biphasic, initially suppressive, later inductive. Furthermore, the phase-locked type-1-fimbrial ON variant of CFT073 inhibited caspase-1 activation and IL-1β release. In addition, the ability of CFT073 to adhere to and invade NLRP3 deficient cells was significantly reduced compare to wild-type cells. The reduced colonization of NLRP3-deficient cells was type-1 fimbriae dependent. In conclusion, we found that the NLRP3 inflammasome was important for type-1 fimbriae-dependent colonization of bladder epithelial cells and that both type-1 fimbriae and α-hemolysin can modulate the activity of the NLRP3 inflammasome.
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影响因子：
11.3
作者：
Hannan TJ;Totsika M;Mansfield KJ;Moore KH;Schembri MA;Hultgren SJ
通讯作者：
Hultgren SJ
DOI：
10.1038/nrmicro3432
发表时间：
2015-05
期刊：
Nature reviews. Microbiology
影响因子：
--
作者：
Flores-Mireles AL;Walker JN;Caparon M;Hultgren SJ
通讯作者：
Hultgren SJ
影响因子：
5.2
作者：
Demirel, Isak;Rangel, Ignacio;Kruse, Robert
通讯作者：
Kruse, Robert
影响因子：
30.5
作者：
Baroja-Mazo, Alberto;Martin-Sanchez, Fatima;Pelegrin, Pablo
通讯作者：
Pelegrin, Pablo
影响因子：
4.6
作者：
Hertting, O;Khalil, A;Brauner, A
通讯作者：
Brauner, A