| The S. Typhimurium effector SopE induces caspase-1 activation in stromal cells to initiate gut inflammation. | |
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MedLine Citation:
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PMID: 19683679 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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In the healthy intestinal mucosa, homeostasis between the immune system and commensal microflora prevents detrimental inflammatory responses. Infection with acute enteropathogens such as Salmonella enterica serovar Typhimurium disturbs this homeostasis and triggers inflammation, but the underlying mechanisms are poorly understood. We found that bacterial delivery or ectopic expression of the S. Typhimurium type III effector protein SopE, a known activator of host cellular Rho GTPases, led to proinflammatory caspase-1 activation and consequent maturation and secretion of the cytokine IL-1beta. In vivo, SopE triggered mucosal inflammation in wild-type but not caspase-1(-/-), IL-1R(-/-), or IL-18(-/-) mice. Bone marrow chimeras indicated that caspase-1 was more important in stromal cells, most likely enterocytes, than in bone marrow-derived cells. SopE-mediated caspase-1 activation in vitro was mediated by cellular Rho GTPases Rac-1 and Cdc42. These findings implicate SopE-driven Rho GTPase-mediated caspase-1 activation in stromal cells as a mechanism eliciting mucosal inflammation during S. Typhimurium infection. |
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Authors:
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Andreas J Müller; Claudia Hoffmann; Marlies Galle; Aeke Van Den Broeke; Mathias Heikenwalder; Laura Falter; Benjamin Misselwitz; Marcus Kremer; Rudi Beyaert; Wolf-Dietrich Hardt |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Cell host & microbe Volume: 6 ISSN: 1934-6069 ISO Abbreviation: Cell Host Microbe Publication Date: 2009 Aug |
Date Detail:
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Created Date: 2009-08-17 Completed Date: 2009-10-09 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101302316 Medline TA: Cell Host Microbe Country: United States |
Other Details:
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Languages: eng Pagination: 125-36 Citation Subset: IM |
Affiliation:
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Institute of Microbiology, D-BIOL, ETH Zürich, Zürich CH-8093, Switzerland. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Bacterial Proteins / metabolism* Caspase 1 / biosynthesis*, deficiency Gastrointestinal Tract / cytology*, microbiology*, pathology Inflammation / pathology* Interleukin-18 / deficiency Interleukin-1beta / secretion Intestinal Mucosa / pathology Mice Mice, Inbred C57BL Mice, Knockout Neuropeptides / metabolism Receptors, Interleukin-1 / deficiency Salmonella typhimurium / pathogenicity* Stromal Cells / microbiology rac GTP-Binding Proteins / metabolism |
| Chemical | |
Reg. No./Substance:
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0/Bacterial Proteins; 0/Interleukin-18; 0/Interleukin-1beta; 0/Neuropeptides; 0/Rac1 protein, mouse; 0/Receptors, Interleukin-1; 0/SopE protein, Salmonella; EC 3.4.22.36/Caspase 1; EC 3.6.5.2/rac GTP-Binding Proteins |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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