{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T01:51:11Z","timestamp":1789869071438,"version":"4.0.1"},"reference-count":64,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[2013,4,1]],"date-time":"2013-04-01T00:00:00Z","timestamp":1364774400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2013,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Infection by the chronic periodontitis-associated pathogen<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Porphyromonas gingivalis<\/jats:named-content>activates a Toll-like receptor 2 (TLR2) response that triggers inflammation in the host but also promotes bacterial persistence. Our aim was to define ligands on the surfaces of intact<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">P. gingivalis<\/jats:named-content>cells that determine its ability to activate TLR2. Molecules previously reported as TLR2 agonists include lipopolysaccharide (LPS), fimbriae, the lipoprotein PG1828, and phosphoceramides. We demonstrate that these molecules do not comprise the major factors responsible for stimulating TLR2 by whole bacterial cells. First,<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">P. gingivalis<\/jats:named-content>mutants devoid of the reported protein agonists, PG1828 and fimbriae, activate TLR2 as strongly as the wild type. Second, two-phase extraction of whole bacteria resulted in a preponderance of TLR2 agonist activity partitioning to the hydrophilic phase, demonstrating that phosphoceramides are not a major TLR2 ligand. Third, analysis of LPS revealed that TLR2 activation is independent of lipid A structural variants. Instead, activation of TLR2 and TLR2\/TLR1 by LPS is in large part due to copurifying molecules that are sensitive to the action of the enzyme lipoprotein lipase. Strikingly, intact<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">P. gingivalis<\/jats:named-content>bacterial cells treated with lipoprotein lipase were attenuated in their ability to activate TLR2. We propose that a novel class of molecules comprised by lipoproteins constitutes the major determinants that confer to<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">P. gingivalis<\/jats:named-content>the ability to stimulate TLR2 signaling.<\/jats:p>","DOI":"10.1128\/iai.01036-12","type":"journal-article","created":{"date-parts":[[2013,2,5]],"date-time":"2013-02-05T02:41:05Z","timestamp":1360032065000},"page":"1277-1286","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":81,"title":["A Novel Class of Lipoprotein Lipase-Sensitive Molecules Mediates Toll-Like Receptor 2 Activation by Porphyromonas gingivalis"],"prefix":"10.1128","volume":"81","author":[{"given":"Sumita","family":"Jain","sequence":"first","affiliation":[{"name":"Department of Periodontics, School of Dentistry, University of Washington, Seattle, Washington, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen R.","family":"Coats","sequence":"additional","affiliation":[{"name":"Department of Periodontics, School of Dentistry, University of Washington, Seattle, Washington, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana M.","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Periodontics, School of Dentistry, University of Washington, Seattle, Washington, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard P.","family":"Darveau","sequence":"additional","affiliation":[{"name":"Department of Periodontics, School of Dentistry, University of Washington, Seattle, Washington, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro2337"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-051X.1998.tb02419.x"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.177.12.8296"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2011.10.006"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.179.4.2349"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0966-842X(00)01845-X"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1003252"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0803852105"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.179.4.2359"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.09.008"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2009.09.018"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/13.7.933"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.169.1.10"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.imbio.2008.02.005"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.63.4.1311-1317.1995"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1099\/00221287-136-2-319"},{"key":"e_1_3_2_18_2","doi-asserted-by":"crossref","first-page":"72","DOI":"10.4049\/jimmunol.120.1.72","article-title":"Immunochemical and biologic studies of the lipopolysaccharide of Bacteroides melaninogenicus subspecies asaccharolyticus","volume":"120","author":"Mansheim BJ","year":"1978","unstructured":"MansheimBJOnderdonkABKasperDL. 1978. 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