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Pseudomonas aeruginosa pilin activates the inflammasome
IL-1β is produced from inactive pro-IL-1β by activation of caspase-1 brought about by a multi-subunit protein platform called the inflammasome. Many bacteria can trigger inflammasome activity through flagellin activation of the host protein NLRC4. However, strains of the common human pathogen Pseudo...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Blackwell Publishing Ltd
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3429865/ https://www.ncbi.nlm.nih.gov/pubmed/20955240 http://dx.doi.org/10.1111/j.1462-5822.2010.01541.x |
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author | Lindestam Arlehamn, Cecilia S Evans, Tom J |
author_facet | Lindestam Arlehamn, Cecilia S Evans, Tom J |
author_sort | Lindestam Arlehamn, Cecilia S |
collection | PubMed |
description | IL-1β is produced from inactive pro-IL-1β by activation of caspase-1 brought about by a multi-subunit protein platform called the inflammasome. Many bacteria can trigger inflammasome activity through flagellin activation of the host protein NLRC4. However, strains of the common human pathogen Pseudomonas aeruginosa lacking flagellin can still activate the inflammasome. We set out to identify what non-flagellin components could produce this activation. Using mass spectroscopy, we identified an inflammasome-activating factor from P. aeruginosa as pilin, the major component of the type IV bacterial pilus. Purified pilin introduced into mouse macrophages by liposomal delivery activated caspase-1 and led to secretion of mature IL-1β, as did recombinant pilin purified from Escherichia coli. This was dependent on caspase-1 but not on the host inflammasome proteins NLRC4, NLRP3 or ASC. Mutants of P. aeruginosa strain PA103 lacking pilin did not activate the inflammasome following infection of macrophages with live bacteria. Type III secretion remained intact in the absence of pili, showing this was not due to a lack of effector delivery. Our observations show pilin is a novel activator of the inflammasome in addition to flagellin and the recently described PrgJ protein family, the basal body rod component of the type III apparatus. |
format | Online Article Text |
id | pubmed-3429865 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | Blackwell Publishing Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-34298652012-08-29 Pseudomonas aeruginosa pilin activates the inflammasome Lindestam Arlehamn, Cecilia S Evans, Tom J Cell Microbiol Original Articles IL-1β is produced from inactive pro-IL-1β by activation of caspase-1 brought about by a multi-subunit protein platform called the inflammasome. Many bacteria can trigger inflammasome activity through flagellin activation of the host protein NLRC4. However, strains of the common human pathogen Pseudomonas aeruginosa lacking flagellin can still activate the inflammasome. We set out to identify what non-flagellin components could produce this activation. Using mass spectroscopy, we identified an inflammasome-activating factor from P. aeruginosa as pilin, the major component of the type IV bacterial pilus. Purified pilin introduced into mouse macrophages by liposomal delivery activated caspase-1 and led to secretion of mature IL-1β, as did recombinant pilin purified from Escherichia coli. This was dependent on caspase-1 but not on the host inflammasome proteins NLRC4, NLRP3 or ASC. Mutants of P. aeruginosa strain PA103 lacking pilin did not activate the inflammasome following infection of macrophages with live bacteria. Type III secretion remained intact in the absence of pili, showing this was not due to a lack of effector delivery. Our observations show pilin is a novel activator of the inflammasome in addition to flagellin and the recently described PrgJ protein family, the basal body rod component of the type III apparatus. Blackwell Publishing Ltd 2011-03 /pmc/articles/PMC3429865/ /pubmed/20955240 http://dx.doi.org/10.1111/j.1462-5822.2010.01541.x Text en © 2010 Blackwell Publishing Ltd http://creativecommons.org/licenses/by/2.5/ Re-use of this article is permitted in accordance with the Creative Commons Deed, Attribution 2.5, which does not permit commercial exploitation. |
spellingShingle | Original Articles Lindestam Arlehamn, Cecilia S Evans, Tom J Pseudomonas aeruginosa pilin activates the inflammasome |
title | Pseudomonas aeruginosa pilin activates the inflammasome |
title_full | Pseudomonas aeruginosa pilin activates the inflammasome |
title_fullStr | Pseudomonas aeruginosa pilin activates the inflammasome |
title_full_unstemmed | Pseudomonas aeruginosa pilin activates the inflammasome |
title_short | Pseudomonas aeruginosa pilin activates the inflammasome |
title_sort | pseudomonas aeruginosa pilin activates the inflammasome |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3429865/ https://www.ncbi.nlm.nih.gov/pubmed/20955240 http://dx.doi.org/10.1111/j.1462-5822.2010.01541.x |
work_keys_str_mv | AT lindestamarlehamncecilias pseudomonasaeruginosapilinactivatestheinflammasome AT evanstomj pseudomonasaeruginosapilinactivatestheinflammasome |