Caspase-11 activates a canonical NLRP3 inflammasome by promoting K+ efflux

Rühl, Sebastian and Broz, Petr. (2015) Caspase-11 activates a canonical NLRP3 inflammasome by promoting K+ efflux. European journal of immunology, 45 (10). pp. 2927-2936.

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Official URL: http://edoc.unibas.ch/39424/

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Recognition of microbe-associated molecular patterns or endogenous danger signals by a subset of cytosolic pattern recognition receptors (PRRs) results in the assembly of multi-protein signaling complexes, so-called inflammasomes. Canonical inflammasomes are assembled by NOD-like receptor (NLR) or PYHIN family members and activate caspase-1, which promotes the induction of pyroptosis and the release of mature interleukin (IL)-1β/-18. Recently a non-canonical inflammasome pathway was discovered which results in caspase-11 activation in response to bacterial lipopolysaccharide (LPS) in the cytosol. Interestingly, caspase-11 induces pyroptosis by itself, but requires NLRP3, the inflammasome adapter ASC and caspase-1 to promote cytokine secretion. Here, we have studied the mechanism by which caspase-11 controls IL-1β secretion. Investigating NLRP3/ASC complex formation, we find that caspase-11 functions upstream of a canonical NLRP3 inflammasome. The activation of NLRP3 by caspase-11 during LPS transfection is a cell-intrinsic process and is independent of the release of danger signals. Furthermore, we show that active caspase-11 leads to a drop of intracellular potassium levels, which is necessary to activate NLRP3. Our study therefore sheds new light on the mechanism of non-canonical inflammasome signaling. This article is protected by copyright. All rights reserved.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Former Organization Units Biozentrum > Infection Biology (Broz)
UniBasel Contributors:Broz, Petr and Rühl, Sebastian
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Wiley-Blackwell - STM
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:30 Jun 2016 10:59
Deposited On:04 May 2016 08:35

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