{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T20:21:23Z","timestamp":1790281283448,"version":"4.1.0"},"reference-count":46,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2010,11,11]],"date-time":"2010-11-11T00:00:00Z","timestamp":1289433600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[2010,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The role of nucleotide\u2010binding oligomerization domain\u20101 (NOD1) and nucleotide\u2010binding oligomerization domain\u20102 (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\u2010killed <jats:italic>Legionella<\/jats:italic> and stimulate NF\u2010\u03bab and IFN\u2010\u03b2 promoter activity using an <jats:italic>in vitro<\/jats:italic> luciferase reporter system. We next infected NOD1\u2010 and NOD2\u2010deficient animals with aerosolized <jats:italic>Legionella pneumophila<\/jats:italic>. At 3 days post infection, <jats:italic>Nod1<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> mice had impaired bacterial clearance compared to WT controls. In addition, at 4\u2009h and 24\u2009h, <jats:italic>Nod1<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> mice had impaired neutrophil recruitment to the alveolar space. In contrast, increased lung neutrophils were seen in the <jats:italic>Nod2<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> animals at 24\u2009h. Analysis of cytokine production at 4\u2009h post infection revealed a significant decrease in proinflammatory cytokines in the <jats:italic>Nod1<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> animals when compared to WT animals. In contrast, increased 4\u2010h proinflammatory cytokines were seen in the <jats:italic>Nod2<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> animals. Furthermore, the lungs of both <jats:italic>Nod1<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> and <jats:italic>Nod2<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> mice had significantly increased pro\u2010inflammatory cytokine levels at 24\u2009h, suggesting possible suppressive roles for later stages of infection. Together, our data suggest that although both NOD1 and NOD2 can detect <jats:italic>Legionella<\/jats:italic>, these receptors modulate the <jats:italic>in vivo<\/jats:italic> pulmonary immune response differently.<\/jats:p>","DOI":"10.1002\/eji.201040518","type":"journal-article","created":{"date-parts":[[2010,9,30]],"date-time":"2010-09-30T08:15:07Z","timestamp":1285834507000},"page":"3519-3527","source":"Crossref","is-referenced-by-count":70,"title":["NOD1 and NOD2 regulation of pulmonary innate immunity to <i>Legionella pneumophila<\/i>"],"prefix":"10.1002","volume":"40","author":[{"given":"William R.","family":"Berrington","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ravi","family":"Iyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard D.","family":"Wells","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly 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