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It is initiated and maintained by a dysbiosis of the bacterial biofilm adjacent to teeth with increased prevalence of Gram\u2010negative microorganisms. Nucleotide\u2010binding oligomerization domain containing 1 (<jats:italic>NOD1<\/jats:italic>) is a member of the Nod\u2010like receptors (<jats:styled-content style=\"fixed-case\">NLR<\/jats:styled-content>s) family of proteins that participate in the activation of the innate immune system, in response to invading bacteria or to bacterial antigens present in the cytoplasm. The specific activating ligand for <jats:styled-content style=\"fixed-case\">NOD<\/jats:styled-content>1 is a bacterial peptidoglycan derived primarily from Gram\u2010negative bacteria. This study assessed the role of <jats:italic><jats:styled-content style=\"fixed-case\">NOD<\/jats:styled-content>1<\/jats:italic> in inflammation\u2010mediated tissue destruction in the context of host\u2013microbe interactions. We used mice with whole\u2010genome deletion of the <jats:italic><jats:styled-content style=\"fixed-case\">NOD<\/jats:styled-content>1<\/jats:italic> gene in a microbe\u2010induced periodontitis model using direct injections of heat\u2010killed Gram\u2010negative or Gram\u2010negative\/Gram\u2010positive bacteria on the gingival tissues. <jats:italic>In vitro<\/jats:italic> experiments using primary bone\u2010marrow\u2010derived macrophages from wild\u2010type and <jats:italic><jats:styled-content style=\"fixed-case\">NOD<\/jats:styled-content>1<\/jats:italic> knockout mice provide insight into the role of <jats:styled-content style=\"fixed-case\">NOD<\/jats:styled-content>1 on the macrophage response to Gram\u2010negative and Gram\u2010negative\/Gram\u2010positive bacteria. Microcomputed tomography analysis indicated that deletion of <jats:italic><jats:styled-content style=\"fixed-case\">NOD<\/jats:styled-content>1<\/jats:italic> significantly aggravated bone resorption induced by Gram\u2010negative bacteria, accompanied by an increase in the numbers of osteoclasts. This effect was significantly attenuated by the association with Gram\u2010positive bacteria. <jats:italic>In vitro<\/jats:italic>, quantitative <jats:styled-content style=\"fixed-case\">PCR<\/jats:styled-content> arrays indicated that stimulation of macrophages with heat\u2010killed Gram\u2010negative bacteria induced the same biological processes in wild\u2010type and <jats:italic><jats:styled-content style=\"fixed-case\">NOD<\/jats:styled-content>1<\/jats:italic>\u2010deficient cells; however, expression of pro\u2010inflammatory mediators was increased in NOD1\u2010deficient cells. These results suggest a bone\u2010sparing role for <jats:italic><jats:styled-content style=\"fixed-case\">NOD<\/jats:styled-content>1<\/jats:italic> in this model.<\/jats:p>","DOI":"10.1111\/imm.12654","type":"journal-article","created":{"date-parts":[[2016,8,2]],"date-time":"2016-08-02T18:00:44Z","timestamp":1470160844000},"page":"374-385","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["<i><scp>NOD<\/scp>1<\/i> in the modulation of host\u2013microbe interactions and inflammatory bone resorption in the periodontal disease model"],"prefix":"10.1111","volume":"149","author":[{"given":"Jo\u00e3o Ant\u00f4nio","family":"Chaves de Souza","sequence":"first","affiliation":[{"name":"Department of Diagnosis and Surgery School of Dentistry at Araraquara Universidade Estadual Paulista (UNESP) Araraquara SP Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sabrina Cruz Tfaile","family":"Frasnelli","sequence":"additional","affiliation":[{"name":"Department of Diagnosis and Surgery School of Dentistry at Araraquara Universidade Estadual Paulista (UNESP) Araraquara SP Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fabiana de Almeida","family":"Curylofo\u2010Zotti","sequence":"additional","affiliation":[{"name":"Department of Diagnosis and Surgery School of Dentistry at Araraquara Universidade Estadual Paulista (UNESP) Araraquara SP Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M\u00e1rio Julio","family":"\u00c1vila\u2010Campos","sequence":"additional","affiliation":[{"name":"Department of Microbiology Biomedical Sciences Institute Universidade de Sao Paulo (USP) Sao Paulo SP Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luis Carlos","family":"Spolid\u00f3rio","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pathology School of Dentistry at Araraquara Universidade Estadual Paulista (UNESP) Araraquara SP Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dario Sim\u00f5es","family":"Zamboni","sequence":"additional","affiliation":[{"name":"Department of Cell &amp; Molecular Biology and Pathological Bioagents School of Medicine at Ribeirao Preto Universidade de Sao Paulo (USP) Ribeirao Preto SP Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dana T.","family":"Graves","sequence":"additional","affiliation":[{"name":"Department of Periodontics School of Dental Medicine University of Pennsylvania Philadelphia PA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1705-5481","authenticated-orcid":false,"suffix":"Jr","given":"Carlos","family":"Rossa","sequence":"additional","affiliation":[{"name":"Department of Diagnosis and Surgery School of Dentistry at Araraquara Universidade Estadual Paulista (UNESP) Araraquara SP 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