Source:http://linkedlifedata.com/resource/pubmed/id/18981137
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
10
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pubmed:dateCreated |
2008-11-4
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pubmed:abstractText |
NOD2/CARD15 mediates innate immune responses to mycobacterial infection. However, its role in the regulation of adaptive immunity has remained unknown. In this study, we examined host defense, T cell responses, and tissue pathology in two models of pulmonary mycobacterial infection, using wild-type and Nod2-deficient mice. During the early phase of aerosol infection with Mycobacterium tuberculosis, Nod2(-/-) mice had similar bacterial counts but reduced inflammatory response on histopathology at 4 and 8 wk postchallenge compared with wild-type animals. These findings were confirmed upon intratracheal infection of mice with attenuated Mycobacterium bovis bacillus Calmette-Guérin. Analysis of the lungs 4 wk after bacillus Calmette-Guérin infection demonstrated that Nod2(-/-) mice had decreased production of type 1 cytokines and reduced recruitment of CD8(+) and CD4(+) T cells. Ag-specific T cell responses in both the spleens and thoracic lymph nodes were diminished in Nod2(-/-) mice, indicating impaired adaptive antimycobacterial immunity. The immune regulatory role of NOD2 was not restricted to the lung since Nod2 disruption also led to reduced type 1 T cell activation following i.m. bacillus Calmette-Guérin infection. To determine the importance of diminished innate and adaptive immunity, we measured bacterial burden 6 mo after aerosol infection with M. tuberculosis and followed a second infected group for assessment of survival. Nod2(-/-) mice had a higher bacterial burden in the lungs 6 mo after infection and succumbed sooner than did wild-type controls. Taken together, these data indicate that NOD2 mediates resistance to mycobacterial infection via both innate and adaptive immunity.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
AIM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
1550-6606
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pubmed:author |
pubmed-author:BehrMarcel AMA,
pubmed-author:CoulombeFrançoisF,
pubmed-author:DivangahiMaziarM,
pubmed-author:FlavellRichard ARA,
pubmed-author:GrosPhilippeP,
pubmed-author:GuillotLoïcL,
pubmed-author:KobayashiKoichi SKS,
pubmed-author:KozakRobertR,
pubmed-author:MostowySergeS,
pubmed-author:VeyrierFrédéricF
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pubmed:issnType |
Electronic
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pubmed:day |
15
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pubmed:volume |
181
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
7157-65
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pubmed:dateRevised |
2011-9-22
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pubmed:meshHeading |
pubmed-meshheading:18981137-Animals,
pubmed-meshheading:18981137-CD4-Positive T-Lymphocytes,
pubmed-meshheading:18981137-CD8-Positive T-Lymphocytes,
pubmed-meshheading:18981137-Chemotaxis, Leukocyte,
pubmed-meshheading:18981137-Cytokines,
pubmed-meshheading:18981137-Flow Cytometry,
pubmed-meshheading:18981137-Immunity, Innate,
pubmed-meshheading:18981137-Lung,
pubmed-meshheading:18981137-Lymphocyte Activation,
pubmed-meshheading:18981137-Macrophages, Alveolar,
pubmed-meshheading:18981137-Mice,
pubmed-meshheading:18981137-Microscopy, Confocal,
pubmed-meshheading:18981137-Mycobacterium tuberculosis,
pubmed-meshheading:18981137-Nod2 Signaling Adaptor Protein,
pubmed-meshheading:18981137-Tuberculosis, Pulmonary
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pubmed:year |
2008
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pubmed:articleTitle |
NOD2-deficient mice have impaired resistance to Mycobacterium tuberculosis infection through defective innate and adaptive immunity.
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pubmed:affiliation |
Department of Medicine, McGill University Health Centre, Montreal, Canada.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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