A critical role for hemolysin in Vibrio fluvialis-induced IL-1β secretion mediated by the NLRP3 inflammasome in macrophages.
A critical role for hemolysin in Vibrio fluvialis-induced IL-1β secretion mediated by the NLRP3 inflammasome in macrophages.
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溶血素在河流弧菌诱导的 IL-1β 分泌中的关键作用由巨噬细胞中的 NLRP3 炎性体介导。
DOI：
10.3389/fmicb.2015.00510
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发表时间：
2015
影响因子：
5.2
通讯作者：
Ren Z
中科院分区：
文献类型：
--
作者：
Song L;Huang Y;Zhao M;Wang Z;Wang S;Sun H;Kan B;Meng G;Liang W;Ren Z
河流弧菌引起人类腹泻，但其发病机制尚未得到充分研究。我们推测河流弧菌分泌的溶血素（VFH）可能通过激活NLRP 3炎性小体诱导IL-1β分泌，从而促进河流弧菌的致病性。为了检验这种可能性，我们构建了VFH突变体和补体菌株，并证明了河流弧菌诱导的人单核细胞THP-1细胞和小鼠巨噬细胞中IL-1β的产生和细胞毒性归因于VFH。为了评估VFH在体内的作用，我们用各种菌株腹腔感染成年C57 BL/6小鼠和口服感染哺乳C57/B6小鼠。与感染突变株的小鼠相比，用108 CFU野生型河流弧菌或含有VFH的无细胞上清液处理的小鼠在腹腔灌洗液或结肠中诱导显著更高的IL-1β产生，而在感染后第5天或24 h未观察到对TNF和IL-6产生的影响。VFH促进结肠病理变化和IL-1β释放，而与河弧菌在结肠中的定殖无关。VFH对pro-IL-1β的合成没有影响，但它触发pro-IL-1β加工成IL-1β。此外，使用缺陷型小鼠品系，我们证实了河流弧菌诱导的IL-1β是通过离体激活Caspase-1和NLRP 3炎性体介导的。共聚焦显微镜表明VFH有助于组织蛋白酶B的释放。此外，河流弧菌诱导的IL-1β分泌需要钾（K+）离子和活性氧的产生。我们的研究结果为VFH在NLRP 3炎性小体激活和响应河流弧菌感染的发病机制中的作用提供了新的证据。总结句子：河流弧菌分泌的溶血素通过激活NLRP 3炎性小体诱导IL-1β分泌，并有助于河流弧菌的致病性。
Vibrio fluvialis causes human diarrhea, but the pathogenesis is not well-studied. We hypothesized that V. fluvialis-secreted hemolysin (VFH) may induce IL-1β secretion through the activation of the NLRP3 inflammasome and contribute to the pathogenicity of V. fluvialis. To examine this possibility, we constructed VFH mutant and complement strains and demonstrated that V. fluvialis-induced IL-1β production and cytotoxicity in human monocytic THP-1 cells and mouse macrophages is attributed to VFH. To evaluate the role of VFH in vivo, we infected adult C57BL/6 mice intraperitoneally and suckling C57/B6 mice orally with various strains. The mice treated with 108 CFU wild-type V. fluvialis or cell-free supernatant containing VFH induced significantly higher IL-1β production in peritoneal lavage fluid or in colon compared with those infected with the mutant strain, while no effect on TNF and IL-6 production was observed at day 5 or 24 h post-infection. VFH contributed to pathological changes and IL-1β release independent of colonization of V. fluvialis in the colon. VFH has no effect on the synthesis of pro-IL-1β, but rather it triggers the processing of pro-IL-1β into IL-1β. Furthermore, using deficient mouse strains, we verified that V. fluvialis-induced IL-1β is mediated through activation of Caspase-1 and the NLRP3 inflammasome ex vivo. Confocal microscopy suggests that VFH contributes to cathepsin B release. Furthermore, V. fluvialis-induced IL-1β secretion requires potassium (K+) efflux and reactive oxygen species production. Our results provide new evidence for the role of VFH in the activation of the NLRP3 inflammasome and pathogenesis in response to V. fluvialis infection. Summary Sentence: Vibrio fluvialis-secreted hemolysin induces IL-1β secretion through the activation of the NLRP3 inflammasome and contributes to the pathogenicity of V. fluvialis.
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影响因子：
6.4
作者：
LEVINE, WC;GRIFFIN, PM;TAYLOR, JP
通讯作者：
TAYLOR, JP
DOI：
10.3390/ijerph7103628
发表时间：
2010-10
影响因子：
--
作者：
Igbinosa EO;Okoh AI
通讯作者：
Okoh AI
影响因子：
5.5
作者：
Holzinger, Dirk;Gieldon, Laura;Loeffler, Bettina
通讯作者：
Loeffler, Bettina
影响因子：
64.5
作者：
Gurcel, Laure;Abrami, Laurence;van der Goot, F. Gisou
通讯作者：
van der Goot, F. Gisou
链球菌为链球菌激活NLRP3炎症体需要链霉菌素O和NF-kappa B激活，但与TLR信号传导和P2X7受体无关进行。
DOI：
10.4049/jimmunol.0900444
发表时间：
2009-11-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Harder J;Franchi L;Muñoz-Planillo R;Park JH;Reimer T;Núñez G
通讯作者：
Núñez G