| A specific gene expression program triggered by Gram-positive bacteria in the cytosol. | |
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MedLine Citation:
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PMID: 15269347 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Innate and adaptive immunity depends critically on host recognition of pathogen-associated molecules. Toll-like receptors (TLRs) are key mediators of pathogen surveillance at the cell or phagocytic vacuole surface. However, mechanisms underlying recognition of pathogens in other cellular compartments remain unclear, and responses elicited by cytosolic challenge are poorly characterized. We therefore used mouse cDNA microarrays to investigate gene expression triggered by infection of bone marrow-derived macrophages with cytosol- and vacuole-localized Listeria monocytogenes (Lm), a model cytosolic pathogen. The resulting gene expression program included two basic categories of induced genes: an "early/persistent" cluster consistent with NF-kappaB-dependent responses downstream of TLRs, and a subsequent "late response" cluster largely composed of IFN-responsive genes (IRGs). The early/persistent cluster was observed upon infection with WT, heat-killed, or mutant Lm lacking listeriolysin O, the pore-forming hemolysin that promotes escape from phagocytic vacuoles. However, the IRG cluster depended on entry of WT Lm into the cytosol. Infection with listeriolysin O-expressing, cytosolic Bacillus subtilis (Bs) strikingly recapitulated the expression profile associated with WT Lm, including IRG induction. IRG up-regulation was associated with MyD88-independent induction of IFN-beta transcription and activity. Whereas Staphylococcus aureus (Sa) lipoteichoic acid treatment confirmed that many late-response genes could also be stimulated through TLRs, our study identified a cytosol-specific transcriptional program independent of TLR signaling through MyD88. Further characterization of cytosolic surveillance pathway(s) and their points of convergence with TLR- and IFN-dependent pathways will enhance our understanding of the means by which mammals detect and respond to pathogens. |
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Authors:
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Ramona L McCaffrey; Paul Fawcett; Mary O'Riordan; Kyung-Dall Lee; Edward A Havell; Patrick O Brown; Daniel A Portnoy |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S. Date: 2004-07-21 |
Journal Detail:
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Title: Proceedings of the National Academy of Sciences of the United States of America Volume: 101 ISSN: 0027-8424 ISO Abbreviation: Proc. Natl. Acad. Sci. U.S.A. Publication Date: 2004 Aug |
Date Detail:
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Created Date: 2004-08-04 Completed Date: 2004-09-10 Revised Date: 2009-11-18 |
Medline Journal Info:
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Nlm Unique ID: 7505876 Medline TA: Proc Natl Acad Sci U S A Country: United States |
Other Details:
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Languages: eng Pagination: 11386-91 Citation Subset: IM |
Affiliation:
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Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720-3202, 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 Animals Antigens, Differentiation / genetics Bacillus subtilis / genetics Cell Cycle / physiology Cytosol / microbiology, physiology Female Gene Expression Regulation, Bacterial / physiology* Interferons / physiology Listeria Infections / microbiology* Listeria monocytogenes / genetics* Macrophages / microbiology Membrane Glycoproteins / metabolism Mice Mice, Mutant Strains Myeloid Differentiation Factor 88 NF-kappa B / metabolism Oligonucleotide Array Sequence Analysis* Receptors, Cell Surface / metabolism Receptors, Immunologic / genetics Staphylococcus aureus / genetics Toll-Like Receptors Transcription, Genetic / physiology Vacuoles / microbiology, physiology |
| Grant Support | |
ID/Acronym/Agency:
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F31 AI50250-01/AI/NIAID NIH HHS; R01 AI127655/AI/NIAID NIH HHS; R01 CA77097/CA/NCI NIH HHS; R37 AI029619/AI/NIAID NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Adaptor Proteins, Signal Transducing; 0/Antigens, Differentiation; 0/Membrane Glycoproteins; 0/Myd88 protein, mouse; 0/Myeloid Differentiation Factor 88; 0/NF-kappa B; 0/Receptors, Cell Surface; 0/Receptors, Immunologic; 0/Toll-Like Receptors; 9008-11-1/Interferons |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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