Publication Date:
2014-04-18
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Meunier, Etienne -- Dick, Mathias S -- Dreier, Roland F -- Schurmann, Nura -- Kenzelmann Broz, Daniela -- Warming, Soren -- Roose-Girma, Merone -- Bumann, Dirk -- Kayagaki, Nobuhiko -- Takeda, Kiyoshi -- Yamamoto, Masahiro -- Broz, Petr -- England -- Nature. 2014 May 15;509(7500):366-70. doi: 10.1038/nature13157. Epub 2014 Apr 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Focal Area Infection Biology, Biozentrum, University of Basel, CH-4056 Basel, Switzerland. ; 1] Focal Area Infection Biology, Biozentrum, University of Basel, CH-4056 Basel, Switzerland [2]. ; Department Biomedicine, University of Basel, CH-4056 Basel, Switzerland. ; Genentech Inc., South San Francisco, California 94080, USA. ; Department of Microbiology and Immunology, Osaka University, Yamadaoka, Suita, Osaka 565-0871, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24739961" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Autophagy/immunology
;
Caspases/*metabolism
;
Cytosol/microbiology
;
Enzyme Activation
;
GTP Phosphohydrolases/*metabolism
;
Galectins/immunology
;
Gram-Negative Bacteria/growth & development/*immunology/pathogenicity
;
Immunity, Innate/immunology
;
Inflammasomes/immunology/*metabolism
;
Interferon Type I/*immunology
;
Lipopolysaccharides/immunology
;
Mice
;
Phagosomes/immunology/microbiology
;
Salmonella typhimurium/growth & development/immunology
;
Vacuoles/*microbiology
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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