Pseudomonas aeruginosa pilin activates the inflammasome

Lindestam Arlehamn, C.S. and Evans, T.J. (2011) Pseudomonas aeruginosa pilin activates the inflammasome. Cellular Microbiology, 13(3), pp. 388-401. (doi: 10.1111/j.1462-5822.2010.01541.x) (PMID:20955240) (PMCID:PMC3429865)

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Abstract

IL-1 beta is produced from inactive pro-IL-1 beta 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-1 beta, 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

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Evans, Professor Tom
Authors: Lindestam Arlehamn, C.S., and Evans, T.J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Cellular Microbiology
Publisher:Blackwell Publishing
ISSN:1462-5814
ISSN (Online):1462-5822
Published Online:03 November 2010
Copyright Holders:Copyright © 2010 Blackwell Publishing Ltd
First Published:First published in Cellular Microbiology 13(3):388-410
Publisher Policy:reproduced in accordance with the publisher policy

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