Cargando…

A critical role for hemolysin in Vibrio fluvialis-induced IL-1β secretion mediated by the NLRP3 inflammasome in macrophages

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, w...

Descripción completa

Detalles Bibliográficos
Autores principales: Song, Liqiong, Huang, Yuanming, Zhao, Meng, Wang, Zhihao, Wang, Shujing, Sun, Hui, Kan, Biao, Meng, Guangxun, Liang, Weili, Ren, Zhihong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4440915/
https://www.ncbi.nlm.nih.gov/pubmed/26052324
http://dx.doi.org/10.3389/fmicb.2015.00510
_version_ 1782372712560197632
author Song, Liqiong
Huang, Yuanming
Zhao, Meng
Wang, Zhihao
Wang, Shujing
Sun, Hui
Kan, Biao
Meng, Guangxun
Liang, Weili
Ren, Zhihong
author_facet Song, Liqiong
Huang, Yuanming
Zhao, Meng
Wang, Zhihao
Wang, Shujing
Sun, Hui
Kan, Biao
Meng, Guangxun
Liang, Weili
Ren, Zhihong
author_sort Song, Liqiong
collection PubMed
description 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 10(8) 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.
format Online
Article
Text
id pubmed-4440915
institution National Center for Biotechnology Information
language English
publishDate 2015
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-44409152015-06-05 A critical role for hemolysin in Vibrio fluvialis-induced IL-1β secretion mediated by the NLRP3 inflammasome in macrophages Song, Liqiong Huang, Yuanming Zhao, Meng Wang, Zhihao Wang, Shujing Sun, Hui Kan, Biao Meng, Guangxun Liang, Weili Ren, Zhihong Front Microbiol Microbiology 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 10(8) 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. Frontiers Media S.A. 2015-05-22 /pmc/articles/PMC4440915/ /pubmed/26052324 http://dx.doi.org/10.3389/fmicb.2015.00510 Text en Copyright © 2015 Song, Huang, Zhao, Wang, Wang, Sun, Kan, Meng, Liang and Ren. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Microbiology
Song, Liqiong
Huang, Yuanming
Zhao, Meng
Wang, Zhihao
Wang, Shujing
Sun, Hui
Kan, Biao
Meng, Guangxun
Liang, Weili
Ren, Zhihong
A critical role for hemolysin in Vibrio fluvialis-induced IL-1β secretion mediated by the NLRP3 inflammasome in macrophages
title A critical role for hemolysin in Vibrio fluvialis-induced IL-1β secretion mediated by the NLRP3 inflammasome in macrophages
title_full A critical role for hemolysin in Vibrio fluvialis-induced IL-1β secretion mediated by the NLRP3 inflammasome in macrophages
title_fullStr A critical role for hemolysin in Vibrio fluvialis-induced IL-1β secretion mediated by the NLRP3 inflammasome in macrophages
title_full_unstemmed A critical role for hemolysin in Vibrio fluvialis-induced IL-1β secretion mediated by the NLRP3 inflammasome in macrophages
title_short A critical role for hemolysin in Vibrio fluvialis-induced IL-1β secretion mediated by the NLRP3 inflammasome in macrophages
title_sort critical role for hemolysin in vibrio fluvialis-induced il-1β secretion mediated by the nlrp3 inflammasome in macrophages
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4440915/
https://www.ncbi.nlm.nih.gov/pubmed/26052324
http://dx.doi.org/10.3389/fmicb.2015.00510
work_keys_str_mv AT songliqiong acriticalroleforhemolysininvibriofluvialisinducedil1bsecretionmediatedbythenlrp3inflammasomeinmacrophages
AT huangyuanming acriticalroleforhemolysininvibriofluvialisinducedil1bsecretionmediatedbythenlrp3inflammasomeinmacrophages
AT zhaomeng acriticalroleforhemolysininvibriofluvialisinducedil1bsecretionmediatedbythenlrp3inflammasomeinmacrophages
AT wangzhihao acriticalroleforhemolysininvibriofluvialisinducedil1bsecretionmediatedbythenlrp3inflammasomeinmacrophages
AT wangshujing acriticalroleforhemolysininvibriofluvialisinducedil1bsecretionmediatedbythenlrp3inflammasomeinmacrophages
AT sunhui acriticalroleforhemolysininvibriofluvialisinducedil1bsecretionmediatedbythenlrp3inflammasomeinmacrophages
AT kanbiao acriticalroleforhemolysininvibriofluvialisinducedil1bsecretionmediatedbythenlrp3inflammasomeinmacrophages
AT mengguangxun acriticalroleforhemolysininvibriofluvialisinducedil1bsecretionmediatedbythenlrp3inflammasomeinmacrophages
AT liangweili acriticalroleforhemolysininvibriofluvialisinducedil1bsecretionmediatedbythenlrp3inflammasomeinmacrophages
AT renzhihong acriticalroleforhemolysininvibriofluvialisinducedil1bsecretionmediatedbythenlrp3inflammasomeinmacrophages
AT songliqiong criticalroleforhemolysininvibriofluvialisinducedil1bsecretionmediatedbythenlrp3inflammasomeinmacrophages
AT huangyuanming criticalroleforhemolysininvibriofluvialisinducedil1bsecretionmediatedbythenlrp3inflammasomeinmacrophages
AT zhaomeng criticalroleforhemolysininvibriofluvialisinducedil1bsecretionmediatedbythenlrp3inflammasomeinmacrophages
AT wangzhihao criticalroleforhemolysininvibriofluvialisinducedil1bsecretionmediatedbythenlrp3inflammasomeinmacrophages
AT wangshujing criticalroleforhemolysininvibriofluvialisinducedil1bsecretionmediatedbythenlrp3inflammasomeinmacrophages
AT sunhui criticalroleforhemolysininvibriofluvialisinducedil1bsecretionmediatedbythenlrp3inflammasomeinmacrophages
AT kanbiao criticalroleforhemolysininvibriofluvialisinducedil1bsecretionmediatedbythenlrp3inflammasomeinmacrophages
AT mengguangxun criticalroleforhemolysininvibriofluvialisinducedil1bsecretionmediatedbythenlrp3inflammasomeinmacrophages
AT liangweili criticalroleforhemolysininvibriofluvialisinducedil1bsecretionmediatedbythenlrp3inflammasomeinmacrophages
AT renzhihong criticalroleforhemolysininvibriofluvialisinducedil1bsecretionmediatedbythenlrp3inflammasomeinmacrophages