{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T10:31:53Z","timestamp":1761129113610,"version":"3.40.2"},"reference-count":47,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2014,1,1]],"date-time":"2014-01-01T00:00:00Z","timestamp":1388534400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Nucleotide-binding oligomerization domain 2 (NOD2) is a cytosolic pathogen recognition receptor that regulates susceptibility to a variety of infections and chronic diseases. Burkholderia pseudomallei, a facultative intracellular bacterium, causes the tropical infection melioidosis. We hypothesized that NOD2 may participate in host defense in melioidosis. We performed a series of in vitro assays and in vivo experiments and analyzed the association of human genetic variation with infection to delineate the contribution of NOD2 to the host response to B. pseudomallei. We found that transfection with NOD2 mediated NF-\u03baB activation induced by B. pseudomallei stimulation of HEK293 cells. After low-dose inoculation with aerosolized B. pseudomallei, Nod2-deficient mice showed impaired clinical responses and permitted greater bacterial replication in the lung and dissemination to the spleen compared with wild-type mice. IL-6 and KC levels were higher in the lungs of Nod2-deficient mice. In a cohort of 1562 Thai subjects, a common genetic polymorphism in the NOD2 region, rs7194886, was associated with melioidosis, and this effect was most pronounced in women. rs7194886 was not associated with differences in cytokine production induced by whole-blood stimulation with the NOD2 ligand, muramyl dipeptide, or B. pseudomallei. To our knowledge, these findings are the first to characterize the role of NOD2 in host defense in mammalian melioidosis.<\/jats:p>","DOI":"10.4049\/jimmunol.1301436","type":"journal-article","created":{"date-parts":[[2013,12,3]],"date-time":"2013-12-03T04:56:44Z","timestamp":1386046604000},"page":"300-307","source":"Crossref","is-referenced-by-count":12,"title":["The Role of NOD2 in Murine and Human Melioidosis"],"prefix":"10.1093","volume":"192","author":[{"given":"Nicolle D","family":"Myers","sequence":"first","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Washington School of Medicine , Seattle, WA 98195"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Narisara","family":"Chantratita","sequence":"additional","affiliation":[{"name":"Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University , Bangkok 10400,","place":["Thailand"]},{"name":"Department of Microbiology and Immunology, Faculty of Tropical Medicine, Mahidol University , Bangkok 10400,","place":["Thailand"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William R","family":"Berrington","sequence":"additional","affiliation":[{"name":"Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington School of Medicine , Seattle, WA 98195"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wirongrong","family":"Chierakul","sequence":"additional","affiliation":[{"name":"Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University , Bangkok 10400,","place":["Thailand"]},{"name":"Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University , Bangkok 10400,","place":["Thailand"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Direk","family":"Limmathurotsakul","sequence":"additional","affiliation":[{"name":"Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University , Bangkok 10400,","place":["Thailand"]},{"name":"Department of Tropical Hygiene, Faculty of Tropical Medicine, Mahidol University , Bangkok 10400,","place":["Thailand"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vanaporn","family":"Wuthiekanun","sequence":"additional","affiliation":[{"name":"Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University , Bangkok 10400,","place":["Thailand"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johanna D","family":"Robertson","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Washington School of Medicine , Seattle, WA 98195"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H Denny","family":"Liggitt","sequence":"additional","affiliation":[{"name":"Department of Comparative Medicine, University of Washington School of Medicine , Seattle, WA 98195"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sharon J","family":"Peacock","sequence":"additional","affiliation":[{"name":"Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University , Bangkok 10400,","place":["Thailand"]},{"name":"Department of Microbiology and Immunology, Faculty of Tropical Medicine, Mahidol University , Bangkok 10400,","place":["Thailand"]},{"name":"Department of Medicine, University of Cambridge, Addenbrooke\u2019s Hospital , Cambridge CB2 2QQ,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shawn J","family":"Skerrett","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Washington School of Medicine , Seattle, WA 98195"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T Eoin","family":"West","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Washington School of Medicine , Seattle, WA 98195"},{"name":"International Respiratory and Severe Illness Center, University of Washington , Seattle, WA 98104"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2014,1,1]]},"reference":[{"key":"2025032404050252800_r1","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1056\/NEJMra1204699","article-title":"Melioidosis","volume":"367","author":"Wiersinga","year":"2012","journal-title":"N. Engl. J. 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Immunol."},{"key":"2025032404050252800_r6","doi-asserted-by":"crossref","first-page":"5612","DOI":"10.1128\/IAI.00618-09","article-title":"Toll-like receptor signaling in airborne Burkholderia thailandensis infection","volume":"77","author":"West","year":"2009","journal-title":"Infect. Immun."},{"key":"2025032404050252800_r7","first-page":"1","article-title":"Intracellular NOD-like receptors in innate immunity, infection and disease","volume":"10","author":"Franchi","year":"2008","journal-title":"Cell. Microbiol."},{"key":"2025032404050252800_r8","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/j.coi.2008.06.001","article-title":"NOD-like receptors (NLRs): bona fide intracellular microbial sensors","volume":"20","author":"Shaw","year":"2008","journal-title":"Curr. Opin. 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