{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T02:36:25Z","timestamp":1791945385795,"version":"4.3.4"},"update-to":[{"DOI":"10.1371\/journal.ppat.1009311","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2021,7,23]],"date-time":"2021-07-23T00:00:00Z","timestamp":1626998400000}}],"reference-count":136,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2021,7,13]],"date-time":"2021-07-13T00:00:00Z","timestamp":1626134400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01 DE025225"],"award-info":[{"award-number":["R01 DE025225"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 DE025225"],"award-info":[{"award-number":["R01 DE025225"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["F30 DE027598"],"award-info":[{"award-number":["F30 DE027598"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["T32DE007306"],"award-info":[{"award-number":["T32DE007306"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    Periodontal disease is driven by dysbiosis in the oral microbiome, resulting in over-representation of species that induce the release of pro-inflammatory cytokines, chemokines, and tissue-remodeling matrix metalloproteinases (MMPs) in the periodontium. These chronic tissue-destructive inflammatory responses result in gradual loss of tooth-supporting alveolar bone. The oral spirochete\n                    <jats:italic>Treponema denticola<\/jats:italic>\n                    , is consistently found at significantly elevated levels in periodontal lesions. Host-expressed Toll-Like Receptor 2 (TLR2) senses a variety of bacterial ligands, including acylated lipopolysaccharides and lipoproteins.\n                    <jats:italic>T<\/jats:italic>\n                    .\n                    <jats:italic>denticola<\/jats:italic>\n                    dentilisin, a surface-expressed protease complex comprised of three lipoproteins has been implicated as a virulence factor in periodontal disease, primarily due to its proteolytic activity. While the role of acylated bacterial components in induction of inflammation is well-studied, little attention has been given to the potential role of the acylated nature of dentilisin. The purpose of this study was to test the hypothesis that\n                    <jats:italic>T<\/jats:italic>\n                    .\n                    <jats:italic>denticola<\/jats:italic>\n                    dentilisin activates a TLR2-dependent mechanism, leading to upregulation of tissue-destructive genes in periodontal tissue. RNA-sequencing of periodontal ligament cells challenged with\n                    <jats:italic>T<\/jats:italic>\n                    .\n                    <jats:italic>denticola<\/jats:italic>\n                    bacteria revealed significant upregulation of genes associated with extracellular matrix organization and degradation including potentially tissue-specific inducible MMPs that may play novel roles in modulating host immune responses that have yet to be characterized within the context of oral disease. The Gram-negative oral commensal,\n                    <jats:italic>Veillonella parvula<\/jats:italic>\n                    , failed to upregulate these same MMPs. Dentilisin-induced upregulation of MMPs was mediated via TLR2 and MyD88 activation, since knockdown of expression of either abrogated these effects. Challenge with purified dentilisin upregulated the same MMPs while a dentilisin-deficient\n                    <jats:italic>T<\/jats:italic>\n                    .\n                    <jats:italic>denticola<\/jats:italic>\n                    mutant had no effect. Finally,\n                    <jats:italic>T<\/jats:italic>\n                    .\n                    <jats:italic>denticola<\/jats:italic>\n                    -mediated activation of TLR2\/MyD88 lead to the nuclear translocation of the transcription factor Sp1, which was shown to be a critical regulator of all\n                    <jats:italic>T<\/jats:italic>\n                    .\n                    <jats:italic>denticola-<\/jats:italic>\n                    dependent MMP expression. Taken together, these data suggest that\n                    <jats:italic>T<\/jats:italic>\n                    .\n                    <jats:italic>denticola<\/jats:italic>\n                    dentilisin stimulates tissue-destructive cellular processes in a TLR2\/MyD88\/Sp1-dependent fashion.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1009311","type":"journal-article","created":{"date-parts":[[2021,7,13]],"date-time":"2021-07-13T14:18:00Z","timestamp":1626185880000},"page":"e1009311","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":27,"title":["Treponema denticola dentilisin triggered TLR2\/MyD88 activation upregulates a tissue destructive program involving MMPs via Sp1 in human oral cells"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7553-155X","authenticated-orcid":true,"given":"Sean","family":"Ganther","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0899-9061","authenticated-orcid":true,"given":"Allan","family":"Radaic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8356-7413","authenticated-orcid":true,"given":"Erin","family":"Malone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pachiyappan","family":"Kamarajan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nai-Yuan Nicholas","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Tafolla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Zhan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7073-7855","authenticated-orcid":true,"given":"J. Christopher","family":"Fenno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1330-0654","authenticated-orcid":true,"given":"Yvonne L.","family":"Kapila","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,7,13]]},"reference":[{"issue":"10","key":"ppat.1009311.ref001","doi-asserted-by":"crossref","first-page":"914","DOI":"10.1177\/0022034512457373","article-title":"Prevalence of Periodontitis in Adults in the United States: 2009 and 2010.","volume":"91","author":"P.I. 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