| Anthrax toxin induces macrophage death by p38 MAPK inhibition but leads to inflammasome activation via ATP leakage. | |
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MedLine Citation:
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PMID: 21683629 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Detection of microbial constituents by membrane associated and cytoplasmic pattern recognition receptors is the essence of innate immunity, leading to activation of protective host responses. However, it is still unclear how immune cells specifically respond to pathogenic bacteria. Using virulent and nonvirulent strains of Bacillus anthracis, we have shown that secretion of ATP by infected macrophages and the sequential activation of the P2X7 purinergic receptor and nucleotide binding oligomerization domain (NOD)-like receptors are critical for IL-1-dependent host protection from virulent B. anthracis. Importantly, lethal toxin produced by virulent B. anthracis blocked activation of protein kinases, p38 MAPK and AKT, resulting in opening of a connexin ATP release channel and induction of macrophage death. Prevention of cell death or ATP release through constitutive p38 or AKT activation interfered with inflammasome activation and IL-1β production, thereby compromising antimicrobial immunity. |
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Authors:
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Syed Raza Ali; Anjuli M Timmer; Sameera Bilgrami; Eek Joong Park; Lars Eckmann; Victor Nizet; Michael Karin |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2011-06-16 |
Journal Detail:
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Title: Immunity Volume: 35 ISSN: 1097-4180 ISO Abbreviation: Immunity Publication Date: 2011 Jul |
Date Detail:
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Created Date: 2011-07-22 Completed Date: 2011-10-04 Revised Date: 2012-02-29 |
Medline Journal Info:
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Nlm Unique ID: 9432918 Medline TA: Immunity Country: United States |
Other Details:
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Languages: eng Pagination: 34-44 Citation Subset: IM |
Copyright Information:
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Copyright © 2011 Elsevier Inc. All rights reserved. |
Affiliation:
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Laboratory of Signal Transduction, Department of Pharmacology, University of California, San Diego, La Jolla, California, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adaptor Proteins, Signal Transducing
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metabolism Adenosine Triphosphate / secretion Animals Anthrax / immunology*, microbiology Antigens, Bacterial / genetics, immunology, metabolism* Apoptosis / drug effects Apoptosis Regulatory Proteins / metabolism Bacillus anthracis / genetics, immunology*, pathogenicity Bacterial Toxins / genetics, immunology, metabolism* Cells, Cultured Connexin 43 / metabolism Immunity, Innate / genetics Inflammasomes / metabolism* Interleukin-1beta / immunology, metabolism Macrophages, Peritoneal / immunology, metabolism*, microbiology, pathology Mice Mice, Inbred C57BL Mutation / genetics Oncogene Protein v-akt / antagonists & inhibitors Receptors, Purinergic P2X7 / metabolism Virulence / genetics p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors |
| Grant Support | |
ID/Acronym/Agency:
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R01 AI043477-15/AI/NIAID NIH HHS; R01 ES006376-19/ES/NIEHS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Adaptor Proteins, Signal Transducing; 0/Antigens, Bacterial; 0/Apoptosis Regulatory Proteins; 0/Bacterial Toxins; 0/Connexin 43; 0/Inflammasomes; 0/Interleukin-1beta; 0/NALP1 protein, mouse; 0/Receptors, Purinergic P2X7; 0/anthrax toxin; 56-65-5/Adenosine Triphosphate; EC 2.7.11.1/Oncogene Protein v-akt; EC 2.7.11.24/p38 Mitogen-Activated Protein Kinases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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