{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T22:21:15Z","timestamp":1782166875242,"version":"3.54.5"},"reference-count":38,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T00:00:00Z","timestamp":1759190400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002848","name":"National Fund for Scientific and Technological Development","doi-asserted-by":"publisher","award":["1220105"],"award-info":[{"award-number":["1220105"]}],"id":[{"id":"10.13039\/501100002848","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002848","name":"National Fund for Scientific and Technological Development","doi-asserted-by":"publisher","award":["11220310"],"award-info":[{"award-number":["11220310"]}],"id":[{"id":"10.13039\/501100002848","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002848","name":"National Fund for Scientific and Technological Development","doi-asserted-by":"publisher","award":["1200098"],"award-info":[{"award-number":["1200098"]}],"id":[{"id":"10.13039\/501100002848","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002848","name":"National Fund for Scientific and Technological Development","doi-asserted-by":"publisher","award":["21221794"],"award-info":[{"award-number":["21221794"]}],"id":[{"id":"10.13039\/501100002848","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["IJMS"],"abstract":"<jats:p>Periodontitis has been associated with adverse pregnancy outcomes, but the effect of oral pathogens on placental tissue and local immunity remains unclear. In this study, we investigated the response of human placental explants (HPEs) to lysates of Porphyromonas (P.) gingivalis, a keystone periodontal pathogen. Exposure to P. gingivalis induced significant histological damage and extracellular matrix degradation in placental tissue. The lysate activated the canonical NF-\u03baB pathway, as demonstrated by increased phosphorylation of I\u03baB\u03b1, particularly in the trophoblast. This activation was predominantly mediated by Toll-like receptor 2 (TLR-2), with partial contribution from TLR-4. Notably, TLR-2 protein levels decreased upon stimulation, while soluble (s) TLR-2 was markedly elevated in culture supernatants, suggesting receptor cleavage as a regulatory mechanism. P. gingivalis also triggered a robust proinflammatory cytokine secretion, including IL-1\u03b2, IL-6, IL-8, and TNF-\u03b1, with variable dependence on TLR-2 and TLR-4 signaling. These findings reveal that P. gingivalis components elicit a complex innate immune response in the placenta, driven by TLR-mediated NF-\u03baB activation and modulated by sTLR-2. This study provides mechanistic insight into how periodontitis may contribute to placental inflammation and highlights potential pathways linking maternal oral health to pregnancy complications.<\/jats:p>","DOI":"10.3390\/ijms26199558","type":"journal-article","created":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T15:38:55Z","timestamp":1759246735000},"page":"9558","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Porphyromonas gingivalis Lysate Induces TLR-2\/4-Dependent NF-\u03baB Activation and Inflammatory Damage in the Human Placental Barrier"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-0433-0791","authenticated-orcid":false,"given":"Sebasti\u00e1n","family":"Araneda-Rojas","sequence":"first","affiliation":[{"name":"Instituto de Ciencias Biom\u00e9dicas (ICBM), Facultad de Medicina, Universidad de Chile, Santiago 8380453, Chile"},{"name":"Departamento de Patolog\u00eda y Medicina Oral y Laboratorio de Biolog\u00eda Periodontal, Facultad de Odontolog\u00eda, Universidad de Chile, Santiago 8380544, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8710-6745","authenticated-orcid":false,"given":"Christian","family":"Castillo","sequence":"additional","affiliation":[{"name":"Instituto de Ciencias Biom\u00e9dicas (ICBM), Facultad de Medicina, Universidad de Chile, Santiago 8380453, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3200-9811","authenticated-orcid":false,"given":"Ana","family":"Liempi","sequence":"additional","affiliation":[{"name":"Instituto de Ciencias Biom\u00e9dicas (ICBM), Facultad de Medicina, Universidad de Chile, Santiago 8380453, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6039-8239","authenticated-orcid":false,"given":"Alejandro","family":"Fern\u00e1ndez-Moya","sequence":"additional","affiliation":[{"name":"Instituto de Ciencias Biom\u00e9dicas (ICBM), Facultad de Medicina, Universidad de Chile, Santiago 8380453, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jes\u00fas","family":"Guerrero-Mu\u00f1oz","sequence":"additional","affiliation":[{"name":"Instituto de Ciencias Biom\u00e9dicas (ICBM), Facultad de Medicina, Universidad de Chile, Santiago 8380453, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebasti\u00e1n","family":"Alfaro","sequence":"additional","affiliation":[{"name":"Instituto de Ciencias Biom\u00e9dicas (ICBM), Facultad de Medicina, Universidad de Chile, Santiago 8380453, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-9468-3213","authenticated-orcid":false,"given":"Christian","family":"Gallardo","sequence":"additional","affiliation":[{"name":"Instituto de Ciencias Biom\u00e9dicas (ICBM), Facultad de Medicina, Universidad de Chile, Santiago 8380453, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roc\u00edo","family":"Arregui","sequence":"additional","affiliation":[{"name":"Instituto de Ciencias Biom\u00e9dicas (ICBM), Facultad de Medicina, Universidad de Chile, Santiago 8380453, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1617-6401","authenticated-orcid":false,"given":"Anilei","family":"Hoare","sequence":"additional","affiliation":[{"name":"Laboratory of Oral Microbiota Ecology, Faculty of Dentistry, Universidad Andres Bello, Santiago 8370133, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Alejandra","family":"Gleisner","sequence":"additional","affiliation":[{"name":"Instituto de Ciencias Biom\u00e9dicas (ICBM), Facultad de Medicina, Universidad de Chile, Santiago 8380453, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8289-7314","authenticated-orcid":false,"given":"Marcela","family":"Hern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Departamento de Patolog\u00eda y Medicina Oral y Laboratorio de Biolog\u00eda Periodontal, Facultad de Odontolog\u00eda, Universidad de Chile, Santiago 8380544, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0201-1665","authenticated-orcid":false,"given":"Ulrike","family":"Kemmerling","sequence":"additional","affiliation":[{"name":"Instituto de Ciencias Biom\u00e9dicas (ICBM), Facultad de Medicina, Universidad de Chile, Santiago 8380453, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Baergen, R.N., Burton, G.J., and Kaplan, C.G. 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