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Caspase-11 activation requires lysis of pathogen-containing vacuoles by IFN-induced GTPases

Meunier, Etienne and Dick, Mathias S. and Dreier, Roland F. and Schürmann, Nura and Kenzelmann Broz, Daniela and Warming, Søren and Roose-Girma, Merone and Bumann, Dirk and Kayagaki, Nobuhiko and Takeda, Kiyoshi and Yamamoto, Masahiro and Broz, Petr. (2014) Caspase-11 activation requires lysis of pathogen-containing vacuoles by IFN-induced GTPases. Nature, 509 (7500). pp. 366-370.

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Official URL: http://edoc.unibas.ch/dok/A6254425

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Abstract

Lipopolysaccharide from Gram-negative bacteria is sensed in the host cell cytoplasm by a non-canonical inflammasome pathway that ultimately results in caspase-11 activation and cell death. In mouse macrophages, activation of this pathway requires the production of type-I interferons, indicating that interferon-induced genes have a critical role in initiating this pathway. Here we report that a cluster of small interferon-inducible GTPases, the so-called guanylate-binding proteins, is required for the full activity of the non-canonical caspase-11 inflammasome during infections with vacuolar Gram-negative bacteria. We show that guanylate-binding proteins are recruited to intracellular bacterial pathogens and are necessary to induce the lysis of the pathogen-containing vacuole. Lysis of the vacuole releases bacteria into the cytosol, thus allowing the detection of their lipopolysaccharide by a yet unknown lipopolysaccharide sensor. Moreover, recognition of the lysed vacuole by the danger sensor galectin-8 initiates the uptake of bacteria into autophagosomes, which results in a reduction of caspase-11 activation. These results indicate that host-mediated lysis of pathogen-containing vacuoles is an essential immune function and is necessary for efficient recognition of pathogens by inflammasome complexes in the cytosol.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Former Organization Units Biozentrum > Infection Biology (Broz)
UniBasel Contributors:Broz, Petr and Meunier, Etienne and Dick, Mathias S. and Dreier, Roland and Schürmann, Nura and Kenzelmann Broz, Daniela and Bumann, Dirk
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Macmillan
ISSN:0028-0836
e-ISSN:1476-4687
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:27 Nov 2017 07:43
Deposited On:18 Jul 2014 09:10

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