{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T17:26:18Z","timestamp":1790270778426,"version":"4.1.0"},"reference-count":75,"publisher":"American Society for Microbiology","issue":"1","license":[{"start":{"date-parts":[[2018,1,1]],"date-time":"2018-01-01T00:00:00Z","timestamp":1514764800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000072","name":"HHS | NIH | National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","award":["R03DE016040"],"award-info":[{"award-number":["R03DE016040"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000072","name":"HHS | NIH | National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","award":["R21 DE022575"],"award-info":[{"award-number":["R21 DE022575"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2018,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            <jats:named-content content-type=\"genus-species\">Treponema denticola<\/jats:named-content>\n            is an indigenous oral spirochete that inhabits the gingival sulcus or periodontal pocket. Increased numbers of oral treponemes within this environment are associated with localized periodontal inflammation, and they are also part of an anaerobic polymicrobial consortium responsible for endodontic infections. Previous studies have indicated that\n            <jats:named-content content-type=\"genus-species\">T. denticola<\/jats:named-content>\n            stimulates the innate immune system through Toll-like receptor 2 (TLR2); however, the pathogen-associated molecular patterns (PAMPs) responsible for\n            <jats:named-content content-type=\"genus-species\">T. denticola<\/jats:named-content>\n            activation of the innate immune system are currently not well defined. In this study, we investigated the role played by\n            <jats:named-content content-type=\"genus-species\">T. denticola<\/jats:named-content>\n            periplasmic flagella (PF), unique motility organelles of spirochetes, in stimulating an innate immune response. Wild-type\n            <jats:named-content content-type=\"genus-species\">T. denticola<\/jats:named-content>\n            stimulated the production of the cytokines tumor necrosis factor alpha (TNF-\u03b1), interleukin-1\u03b2 (IL-1\u03b2), IL-6, IL-10, and IL-12 by monocytes from human peripheral blood mononuclear cells, while its isogenic nonmotile mutant lacking PF resulted in significantly diminished cytokine stimulation. In addition, highly purified PF were able to dose dependently stimulate cytokine TNF-\u03b1, IL-1\u03b2, IL-6, IL-10, and IL-12 production in human monocytes. Wild-type\n            <jats:named-content content-type=\"genus-species\">T. denticola<\/jats:named-content>\n            and the purified PF triggered activation of NF-\u03baB through TLR2, as determined using a variety of TLR-transfected human embryonic 293 cell lines, while the PF-deficient mutants lacked the ability to stimulate, and the complemented PF-positive\n            <jats:named-content content-type=\"genus-species\">T. denticola<\/jats:named-content>\n            strain restored the activation. These findings suggest that\n            <jats:named-content content-type=\"genus-species\">T. denticola<\/jats:named-content>\n            stimulates the innate immune system in a TLR2-dependent fashion and that PF are a key bacterial component involved in this process.\n          <\/jats:p>","DOI":"10.1128\/iai.00573-17","type":"journal-article","created":{"date-parts":[[2017,10,30]],"date-time":"2017-10-30T15:15:16Z","timestamp":1509376516000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":14,"title":["Activation of the Innate Immune System by Treponema denticola Periplasmic Flagella through Toll-Like Receptor 2"],"prefix":"10.1128","volume":"86","author":[{"given":"John","family":"Ruby","sequence":"first","affiliation":[{"name":"Department of Pediatric Dentistry, School of Dentistry, The University of Alabama at Birmingham, Birmingham, Alabama, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Martin","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Louisville School of Medicine, Louisville, Kentucky, USA"},{"name":"Department of Oral Immunology and Infectious Diseases, University of Louisville School of Dentistry, Louisville, Kentucky, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Passineau","sequence":"additional","affiliation":[{"name":"Gene Therapy Program, Allegheny Health Network, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Godovikova","sequence":"additional","affiliation":[{"name":"Department of Biologic and Materials Sciences, School of Dentistry, University of Michigan, Ann Arbor, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Christopher","family":"Fenno","sequence":"additional","affiliation":[{"name":"Department of Biologic and Materials Sciences, School of Dentistry, University of Michigan, Ann Arbor, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Pediatric Dentistry, School of Dentistry, The University of Alabama at Birmingham, Birmingham, Alabama, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1177\/0022034510385242"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0757.2009.00345.x"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-0691.2011.03460.x"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.3402\/jom.v4i0.9929"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/0923-2508(92)90117-7"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1034\/j.1399-302X.1999.140609.x"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.69.10.6276-6283.2001"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0757.2005.00108.x"},{"key":"e_1_3_3_10_2","first-page":"323","volume-title":"Pathogenic Treponema molecular and cellular biology","author":"Holt S","year":"2006","unstructured":"Holt S, Ebersole J. 2006. The oral spirochetes: their ecology and role in the pathogenesis of periodontal disease, p 323\u2013356. In Radolf JD, Lukehart SA (ed), Pathogenic Treponema molecular and cellular biology. Caister Academic Press, Wymondham, Norfolk, UK."},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-051X.1998.tb02419.x"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0757.2006.00179.x"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro2337"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1177\/154405910608500301"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1017\/erm.2013.8"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.02016-08"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00082-12"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2003.10.005"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1863"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/41131"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2010.01.022"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1177\/0022034510381264"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00046-08"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.71.2.717-725.2003"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M010481200"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-302X.2008.00452.x"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00488-09"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01117-07"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1159\/000077867"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2004.09.002"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1385\/IR:33:1:083"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2009.9"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2006.04.036"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-micro-092611-150145"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.174.3.832-840.1992"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.178.12.3664-3667.1996"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.70.4.2233-2237.2002"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.00478-15"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.179.5.1628-1635.1997"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-302X.2007.00404.x"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-6968.1998.tb13325.x"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-051x.2000.027006405.x"},{"key":"e_1_3_3_43_2","first-page":"387","volume-title":"Pathogenic Treponema molecular and cellular biology","author":"Schroder WJ","year":"2006","unstructured":"Schroder WJ, Schumann RR, Gobel UB. 2006. Innate and adaptive immune responses to oral treponemes, p 387\u2013402. In Radolf JD, Lukehart SA (ed), Pathogenic Treponema molecular and cellular biology. Caister Academic Press, Wymondham, Norfolk, UK."},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1177\/10454411980090030101"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1902\/jop.2000.71.10.1535"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.47.33419"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01078-08"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2016.11.005"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01604-06"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1111\/mmi.13544"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2013.10.009"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature10510"},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1306376110"},{"key":"e_1_3_3_54_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2010.01.001"},{"key":"e_1_3_3_55_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.micpath.2016.11.021"},{"key":"e_1_3_3_56_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.14.2.99"},{"key":"e_1_3_3_57_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.15.1.81"},{"key":"e_1_3_3_58_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00173-10"},{"key":"e_1_3_3_59_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.173.19.6101-6109.1991"},{"key":"e_1_3_3_60_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01004-08"},{"key":"e_1_3_3_61_2","doi-asserted-by":"publisher","DOI":"10.1177\/154405910708600102"},{"key":"e_1_3_3_62_2","doi-asserted-by":"publisher","DOI":"10.1177\/08959374940080022001"},{"key":"e_1_3_3_63_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-302X.2007.00335.x"},{"key":"e_1_3_3_64_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.2041-1014.2012.00663.x"},{"key":"e_1_3_3_65_2","doi-asserted-by":"publisher","DOI":"10.1177\/0022034514528212"},{"key":"e_1_3_3_66_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2013.09.001"},{"key":"e_1_3_3_67_2","doi-asserted-by":"publisher","DOI":"10.1111\/omi.12165"},{"key":"e_1_3_3_68_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.177.12.8296"},{"key":"e_1_3_3_69_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1202511"},{"key":"e_1_3_3_70_2","doi-asserted-by":"publisher","DOI":"10.3109\/08820139.2013.822761"},{"key":"e_1_3_3_71_2","doi-asserted-by":"publisher","DOI":"10.1111\/jre.12008"},{"key":"e_1_3_3_72_2","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2012-304635"},{"key":"e_1_3_3_73_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01077-15"},{"key":"e_1_3_3_74_2","doi-asserted-by":"publisher","DOI":"10.1128\/jcm.12.6.792-795.1980"},{"key":"e_1_3_3_75_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.182.23.6698-6706.2000"},{"key":"e_1_3_3_76_2","doi-asserted-by":"publisher","DOI":"10.1089\/hum.2010.069"}],"updated-by":[{"DOI":"10.1128\/iai.00251-18","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2018,6,21]],"date-time":"2018-06-21T00:00:00Z","timestamp":1529539200000}}],"container-title":["Infection and Immunity"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/IAI.00573-17","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/IAI.00573-17","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,5]],"date-time":"2022-03-05T10:47:09Z","timestamp":1646477229000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/IAI.00573-17"}},"subtitle":[],"editor":[{"given":"Marvin","family":"Whiteley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2018,1]]},"references-count":75,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2018,1]]}},"alternative-id":["10.1128\/IAI.00573-17"],"URL":"https:\/\/doi.org\/10.1128\/iai.00573-17","relation":{"correction":[{"id-type":"doi","id":"10.1128\/IAI.00251-18","asserted-by":"object"}]},"ISSN":["0019-9567","1098-5522"],"issn-type":[{"value":"0019-9567","type":"print"},{"value":"1098-5522","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,1]]},"assertion":[{"value":"2017-08-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-10-26","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-12-19","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e00573-17"}}