| NOD1 and NOD2 regulation of pulmonary innate immunity to Legionella pneumophila. | |
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MedLine Citation:
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PMID: 21108472 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The role of nucleotide-binding oligomerization domain-1 (NOD1) and nucleotide-binding oligomerization domain-2 (NOD2), cytoplasmic receptors which detect bacterial cell wall molecules, in pulmonary innate immune responses is poorly understood. We determined that both NOD1 and NOD2 detect heat-killed Legionella and stimulate NF-κb and IFN-β promoter activity using an in vitro luciferase reporter system. We next infected NOD1- and NOD2-deficient animals with aerosolized Legionella pneumophila. At 3 days post infection, Nod1(-/-) mice had impaired bacterial clearance compared to WT controls. In addition, at 4 h and 24 h, Nod1(-/-) mice had impaired neutrophil recruitment to the alveolar space. In contrast, increased lung neutrophils were seen in the Nod2(-/-) animals at 24 h. Analysis of cytokine production at 4 h post infection revealed a significant decrease in proinflammatory cytokines in the Nod1(-/-) animals when compared to WT animals. In contrast, increased 4-h proinflammatory cytokines were seen in the Nod2(-/-) animals. Furthermore, the lungs of both Nod1(-/-) and Nod2(-/-) mice had significantly increased pro-inflammatory cytokine levels at 24 h, suggesting possible suppressive roles for later stages of infection. Together, our data suggest that although both NOD1 and NOD2 can detect Legionella, these receptors modulate the in vivo pulmonary immune response differently. |
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Authors:
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William R Berrington; Ravi Iyer; Richard D Wells; Kelly D Smith; Shawn J Skerrett; Thomas R Hawn |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2010-11-11 |
Journal Detail:
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Title: European journal of immunology Volume: 40 ISSN: 1521-4141 ISO Abbreviation: Eur. J. Immunol. Publication Date: 2010 Dec |
Date Detail:
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Created Date: 2010-11-25 Completed Date: 2011-03-24 Revised Date: 2011-12-21 |
Medline Journal Info:
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Nlm Unique ID: 1273201 Medline TA: Eur J Immunol Country: Germany |
Other Details:
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Languages: eng Pagination: 3519-27 Citation Subset: IM |
Copyright Information:
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Copyright © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. |
Affiliation:
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University of Washington School of Medicine, Seattle, WA 98195-6523, USA. berring@uw.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cell Movement / genetics, immunology Cytokines / metabolism Host-Pathogen Interactions Immunity, Innate Inflammation Mediators / metabolism Interferon-beta / genetics Legionella pneumophila / immunology*, pathogenicity Legionnaires' Disease / immunology* Lung / immunology, metabolism*, pathology Mice Mice, Knockout NF-kappa B / genetics, metabolism Neutrophils / immunology, pathology Nod1 Signaling Adaptor Protein / genetics, immunology, metabolism* Nod2 Signaling Adaptor Protein / genetics, immunology, metabolism* Promoter Regions, Genetic / genetics, immunology Transcriptional Activation / genetics, immunology |
| Grant Support | |
ID/Acronym/Agency:
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K08 AI080952/AI/NIAID NIH HHS; K08 AI080952-01A1/AI/NIAID NIH HHS; R01 AI061464/AI/NIAID NIH HHS; R01 AI061464-01A1/AI/NIAID NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Card15 protein, mouse; 0/Card4 protein, mouse; 0/Cytokines; 0/Inflammation Mediators; 0/NF-kappa B; 0/Nod1 Signaling Adaptor Protein; 0/Nod2 Signaling Adaptor Protein; 77238-31-4/Interferon-beta |
| Comments/Corrections | |
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