{"corpus_id":17392300,"paper_sha":"5ad54ec7a6c0fc8bfc1f511803a10a4afcd25a0f","doi":"10.1371/journal.ppat.1002601","arxiv_id":null,"pmid":22457623,"pmcid":"3310798","mag_id":2088986583,"dblp_id":null,"acl_id":null,"title":"Direct Recognition of Fusobacterium nucleatum by the NK Cell Natural Cytotoxicity Receptor NKp46 Aggravates Periodontal Disease","year":2012,"publication_date":"2012-03-01","venue":"PLoS Pathogens","journal":{"name":"PLoS Pathogens","pages":null,"volume":"8"},"journal_issn":null,"journal_title":null,"publication_types":["JournalArticle"],"pubmed_pub_types":["Journal Article","Research Support, Non-U.S. Gov't"],"s2_fields_of_study":["Biology","Medicine"],"reference_count":70,"citation_count":134,"influential_citation_count":2,"is_open_access":true,"arxiv_categories":null,"arxiv_license":null,"arxiv_journal_ref":null,"mesh_headings":[{"d":"Animals","mj":false,"ui":"D000818"},{"d":"Antigens, Ly","mj":false,"qs":[{"q":"immunology","mj":true,"ui":"Q000276"}],"ui":"D000950"},{"d":"Cells, Cultured","mj":false,"ui":"D002478"},{"d":"Disease Models, Animal","mj":false,"ui":"D004195"},{"d":"Fusobacterium nucleatum","mj":false,"qs":[{"q":"immunology","mj":true,"ui":"Q000276"}],"ui":"D016967"},{"d":"Host-Pathogen Interactions","mj":false,"ui":"D054884"},{"d":"Killer Cells, Natural","mj":false,"qs":[{"q":"immunology","mj":true,"ui":"Q000276"},{"q":"metabolism","mj":false,"ui":"Q000378"}],"ui":"D007694"},{"d":"Mice","mj":false,"ui":"D051379"},{"d":"Mice, Knockout","mj":false,"ui":"D018345"},{"d":"Natural Cytotoxicity Triggering Receptor 1","mj":false,"qs":[{"q":"immunology","mj":true,"ui":"Q000276"}],"ui":"D055627"},{"d":"Periodontitis","mj":false,"qs":[{"q":"immunology","mj":true,"ui":"Q000276"},{"q":"pathology","mj":false,"ui":"Q000473"}],"ui":"D010518"},{"d":"Tumor Necrosis Factor-alpha","mj":false,"qs":[{"q":"metabolism","mj":false,"ui":"Q000378"}],"ui":"D014409"}],"chemicals":[{"n":"Antigens, Ly","ui":"D000950","reg":"0"},{"n":"Natural Cytotoxicity Triggering Receptor 1","ui":"D055627","reg":"0"},{"n":"Ncr1 protein, mouse","ui":"C118384","reg":"0"},{"n":"Tumor Necrosis Factor-alpha","ui":"D014409","reg":"0"}],"comments_corrections":null,"source_flags":5,"s2_open_access_pdf_url":"https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1002601&type=printable","s2_open_access_landing_url":"https://www.semanticscholar.org/paper/5ad54ec7a6c0fc8bfc1f511803a10a4afcd25a0f","s2_open_access_license":"CCBY","s2_open_access_status":"GOLD","pmc_open_access_pdf_url":null,"pmc_open_access_landing_url":null,"pmc_open_access_license":null,"pmc_open_access_status":null,"unpaywall_open_access_pdf_url":null,"unpaywall_open_access_landing_url":null,"unpaywall_open_access_license":null,"unpaywall_open_access_status":null,"abstract":"Periodontitis is a common human chronic inflammatory disease that results in the destruction of the tooth attachment apparatus and tooth loss. Although infections with periopathogenic bacteria such as Porphyromonas gingivalis (P. gingivalis) and Fusobacterium nucleatum (F. nucleatum) are essential for inducing periodontitis, the nature and magnitude of the disease is determined by the host's immune response. Here, we investigate the role played by the NK killer receptor NKp46 (NCR1 in mice), in the pathogenesis of periodontitis. Using an oral infection periodontitis model we demonstrate that following F. nucleatum infection no alveolar bone loss is observed in mice deficient for NCR1 expression, whereas around 20% bone loss is observed in wild type mice and in mice infected with P. gingivalis. By using subcutaneous chambers inoculated with F. nucleatum we demonstrate that immune cells, including NK cells, rapidly accumulate in the chambers and that this leads to a fast and transient, NCR1-dependant TNF-α secretion. We further show that both the mouse NCR1 and the human NKp46 bind directly to F. nucleatum and we demonstrate that this binding is sensitive to heat, to proteinase K and to pronase treatments. Finally, we show in vitro that the interaction of NK cells with F. nucleatum leads to an NCR1-dependent secretion of TNF-α. Thus, the present study provides the first evidence that NCR1 and NKp46 directly recognize a periodontal pathogen and that this interaction influences the outcome of F. nucleatum-mediated periodontitis.","claims":[{"public_id":"cl_378117ef29e5043bb64dce10083dad44","status":"active","text":"Direct recognition of a periodontal pathogen by NCR1 and NKp46 influences the outcome of Fusobacterium nucleatum-mediated periodontitis.","confidence":0.94,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_378117ef29e5043bb64dce10083dad44"},{"public_id":"cl_704b4899ef2a33290b4057d3ad3efe1a","status":"active","text":"Fusobacterium nucleatum recruits immune cells, including NK cells, into subcutaneous chambers and triggers rapid, transient, NCR1-dependent TNF-α secretion.","confidence":0.95,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_704b4899ef2a33290b4057d3ad3efe1a"},{"public_id":"cl_0d84f0a066e381086208dc52c68c36fc","status":"active","text":"Mouse NCR1 and human NKp46 bind directly to Fusobacterium nucleatum, and the binding is sensitive to heat, proteinase K, and pronase treatments.","confidence":0.97,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_0d84f0a066e381086208dc52c68c36fc"},{"public_id":"cl_b45138a56b6ee512677eb4a1613664f0","status":"active","text":"NCR1 deficiency prevents alveolar bone loss after Fusobacterium nucleatum oral infection, whereas wild-type mice show about 20% bone loss.","confidence":0.98,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_b45138a56b6ee512677eb4a1613664f0"},{"public_id":"cl_b55da04047b1dfe9501105aca080c76b","status":"active","text":"NK cell interaction with Fusobacterium nucleatum induces NCR1-dependent TNF-α secretion in vitro.","confidence":0.96,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_b55da04047b1dfe9501105aca080c76b"}],"concepts":[{"public_id":"co_043b06d578ce4e7dbded5bb1e31171b7","status":"active","name":"TNF-α secretion","description":"Release of tumor necrosis factor alpha as a measured inflammatory response.","types":["outcome","cytokine response"],"aliases":["tumor necrosis factor alpha 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