| NOD2 mediates inflammatory responses of primary murine glia to Streptococcus pneumoniae. | |
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MedLine Citation:
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PMID: 20091781 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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It is now widely accepted that resident central nervous system (CNS) cells such as microglia and astrocytes initiate and/or augment inflammation following trauma or infection. However, the mechanisms by which glial cells perceive microbial challenges are only now becoming apparent. We have recently demonstrated that microglia and astrocytes constitutively express nucleotide-binding oligomerization domain-2 (NOD2), a member of the novel nucleotide-binding domain leucine-rich repeat region-containing family of proteins (NLR) that functions as an intracellular receptor for a minimal motif present in all bacterial peptidoglycans. Furthermore, we have shown that this NLR is essential for glial responses to gram-negative pathogens and in vivo CNS inflammation elicited by these organisms. In the present study, we have established that intact Streptococcus pneumoniae, the major causative agent for gram-positive bacterial meningitis in adults, is a potent stimulus for the activation of the pivotal inflammatory transcription factor NF-kB and production of inflammatory cytokines in primary murine microglia and astrocytes. We demonstrate that NOD2 is essential for the maximal responses of these cells to intact S. pneumoniae but not cellular lysates. Finally, we have shown that this cytosolic pattern recognition receptor is required for the elevated inflammatory mediator levels, astrogliosis, and demyelination, following in vivo administration of this gram-positive CNS pathogen. As such, we suggest that NOD2 plays a critical role in the establishment of the lethal inflammation associated with streptococcal meningitis. |
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Authors:
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Xinjie Liu; Vinita S Chauhan; Amy B Young; Ian Marriott |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural |
Journal Detail:
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Title: Glia Volume: 58 ISSN: 1098-1136 ISO Abbreviation: Glia Publication Date: 2010 May |
Date Detail:
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Created Date: 2010-04-08 Completed Date: 2010-06-29 Revised Date: 2011-09-26 |
Medline Journal Info:
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Nlm Unique ID: 8806785 Medline TA: Glia Country: United States |
Other Details:
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Languages: eng Pagination: 839-47 Citation Subset: IM |
Affiliation:
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Department of Pediatrics, Qilu Hospital, Shandong University, Jinan, Shandong, People's Republic of China. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Astrocytes / immunology, metabolism Cells, Cultured Cytokines / metabolism Encephalitis / immunology*, microbiology*, physiopathology Gliosis / immunology*, microbiology*, physiopathology Inflammation Mediators / metabolism Meningitis, Bacterial / immunology, metabolism, physiopathology Mice Mice, Knockout Microglia / immunology, metabolism NF-kappa B / metabolism Nod2 Signaling Adaptor Protein / metabolism* Streptococcal Infections / immunology*, physiopathology |
| Grant Support | |
ID/Acronym/Agency:
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NS050325/NS/NINDS NIH HHS; NS057434/NS/NINDS NIH HHS; R01 NS050325-04/NS/NINDS NIH HHS; R03 NS057434-02S1/NS/NINDS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Card15 protein, mouse; 0/Cytokines; 0/Inflammation Mediators; 0/NF-kappa B; 0/Nod2 Signaling Adaptor Protein |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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