| Phagosomal retention of Francisella tularensis results in TIRAP/Mal-independent TLR2 signaling. | |
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MedLine Citation:
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PMID: 19889726 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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TLR2 plays a central role in the activation of innate immunity in response to Ft, the causative agent of tularemia. We reported previously that Ft LVS elicited strong, dose-dependent NF-kappaB reporter activity in TLR2-expressing human embryo kidney 293 T cells and that Ft LVS-induced murine macrophage proinflammatory cytokine gene and protein expression is TLR2-dependent. We demonstrated further that Ft can signal through TLR2 from within the phagosome and that phagosomal retention of Ft leads to greatly increased expression of a subset of proinflammatory genes. The two adaptor proteins associated with TLR2-mediated signaling are MyD88 and TIRAP. Although MyD88 is absolutely required for the Ft-induced macrophage cytokine response, the requirement for TIRAP can be overcome through retention of Ft within the phagosome. TIRAP-independent signaling was observed whether Ft was retained in the phagosome as a result of bacterial mutation (LVSDeltaiglC) or BFA-mediated inhibition of phagosome acidification. The requirement for TIRAP in TLR2 signaling could also be overcome by increasing the concentrations of synthetic bacterial TLR2 agonists. Taken together, these data suggest that prolonging or enhancing the interaction between TLR2 and its agonist overcomes the "bridging" function ascribed previously to TIRAP. |
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Authors:
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Leah E Cole; Michelle H W Laird; Anna Seekatz; Araceli Santiago; Zhaozhao Jiang; Eileen Barry; Kari Ann Shirey; Katherine A Fitzgerald; Stefanie N Vogel |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2009-11-04 |
Journal Detail:
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Title: Journal of leukocyte biology Volume: 87 ISSN: 1938-3673 ISO Abbreviation: J. Leukoc. Biol. Publication Date: 2010 Feb |
Date Detail:
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Created Date: 2010-02-03 Completed Date: 2010-02-25 Revised Date: 2011-07-22 |
Medline Journal Info:
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Nlm Unique ID: 8405628 Medline TA: J Leukoc Biol Country: United States |
Other Details:
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Languages: eng Pagination: 275-81 Citation Subset: IM |
Affiliation:
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Department of Microbiology and Immunology, University of Maryland, Baltimore, Baltimore, MD 21201, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cell Line Cytokines / genetics, immunology Francisella tularensis / genetics, immunology* Gene Expression Regulation / genetics, immunology Humans Inflammation / genetics, immunology, microbiology Macrophages, Peritoneal / immunology*, microbiology Membrane Glycoproteins / genetics, immunology* Membrane Transport Proteins / genetics, immunology* Mice Mice, Knockout Mutation Myelin Proteins / genetics, immunology* Myeloid Differentiation Factor 88 / genetics, immunology Phagosomes / genetics, immunology*, microbiology Proteolipids / genetics, immunology* Receptors, Interleukin-1 / genetics, immunology* Signal Transduction / genetics, immunology* Toll-Like Receptor 2 / agonists, genetics, immunology* |
| Grant Support | |
ID/Acronym/Agency:
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AI-067497/AI/NIAID NIH HHS; R01 AI018797-29/AI/NIAID NIH HHS; U54 AI-157168/AI/NIAID NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Cytokines; 0/MAL protein, T-cell; 0/Membrane Glycoproteins; 0/Membrane Transport Proteins; 0/Myd88 protein, mouse; 0/Myelin Proteins; 0/Myeloid Differentiation Factor 88; 0/Proteolipids; 0/Receptors, Interleukin-1; 0/TIRAP protein, mouse; 0/Tlr2 protein, mouse; 0/Toll-Like Receptor 2 |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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