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Growth inhibition of cytosolic Salmonella by caspase-1 and caspase-11 precedes host cell death

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Title: Growth inhibition of cytosolic Salmonella by caspase-1 and caspase-11 precedes host cell death
Author(s): Thurston, T
Matthews, S
Jennings, E
Alix, E
Shao, F
Shenoy, A
Birrell, M
Holden, D
Item Type: Journal Article
Abstract: Sensing bacterial products in the cytosol of mammalian cells by NOD-like receptors leads to the activation of caspase-1 inflammasomes, and the production of the pro-inflammatory cytokines interleukin (IL)-18 and IL-1β. In addition, mouse caspase-11 (represented in humans by its orthologs, caspase-4 and caspase-5) detects cytosolic bacterial LPS directly. Activation of caspase-1 and caspase-11 initiates pyroptotic host cell death that releases potentially harmful bacteria from the nutrient-rich host cell cytosol into the extracellular environment. Here we use single cell analysis and time-lapse microscopy to identify a subpopulation of host cells, in which growth of cytosolic Salmonella Typhimurium is inhibited independently or prior to the onset of cell death. The enzymatic activities of caspase-1 and caspase-11 are required for growth inhibition in different cell types. Our results reveal that these proteases have important functions beyond the direct induction of pyroptosis and proinflammatory cytokine secretion in the control of growth and elimination of cytosolic bacteria.
Publication Date: 3-Nov-2016
Date of Acceptance: 19-Sep-2016
URI: http://hdl.handle.net/10044/1/42306
DOI: http://dx.doi.org/10.1038/ncomms13292
ISSN: 2041-1723
Publisher: Nature Publishing Group
Journal / Book Title: Nature Communications
Volume: 7
Sponsor/Funder: The Leverhulme Trust
Funder's Grant Number: ECF-2012-284
Copyright Statement: This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
Keywords: MD Multidisciplinary
Publication Status: Published
Article Number: 13292
Appears in Collections:Airway Disease
Department of Medicine
Faculty of Medicine



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