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Publication : NOD1 and NOD2 regulation of pulmonary innate immunity to Legionella pneumophila.

First Author  Berrington WR Year  2010
Journal  Eur J Immunol Volume  40
Issue  12 Pages  3519-27
PubMed ID  21108472 Mgi Jnum  J:174576
Mgi Id  MGI:5139984 Doi  10.1002/eji.201040518
Citation  Berrington WR, et al. (2010) NOD1 and NOD2 regulation of pulmonary innate immunity to Legionella pneumophila. Eur J Immunol 40(12):3519-27
abstractText  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-kappab and IFN-beta 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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