{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T19:10:43Z","timestamp":1789758643276,"version":"4.0.1"},"update-to":[{"DOI":"10.1371\/journal.ppat.1014574","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T00:00:00Z","timestamp":1789689600000}}],"reference-count":127,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:00:00Z","timestamp":1789430400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","award":["DE028307"],"award-info":[{"award-number":["DE028307"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","award":["DE029400"],"award-info":[{"award-number":["DE029400"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","award":["R03DE032392"],"award-info":[{"award-number":["R03DE032392"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","award":["DE023526"],"award-info":[{"award-number":["DE023526"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000052","name":"NIH Office of the Director","doi-asserted-by":"publisher","award":["OD025204"],"award-info":[{"award-number":["OD025204"]}],"id":[{"id":"10.13039\/100000052","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","award":["T32DE023526"],"award-info":[{"award-number":["T32DE023526"]}],"id":[{"id":"10.13039\/100000072","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 a chronic inflammatory condition that develops in response to oral microbiome dysbiosis and host-microbiome immune response dysregulation. The innate immune system plays a major role in the development and persistence of disease, in part by producing inflammatory cytokines. One of the major cytokines implicated in disease is interleukin-1\u03b2 (IL-1\u03b2), which requires inflammasome activation. Much of the oral microbiome, including Streptococci, which are otherwise considered commensal, is required for the full development of periodontal disease. We have previously reported that inflammatory-activated macrophages and neutrophils counterintuitively allow survival of internalized\n                    <jats:italic>Streptococcus gordonii<\/jats:italic>\n                    over non-activated phagocytes. This internal bacterial survival leads to inflammasome activation via the cytoplasmic activator NLRP6, but not NLRP3, and subsequent increases in IL-1\u03b2 release. Here, we test and find that the keystone pathogen\n                    <jats:italic>Porphyromonas gingivalis<\/jats:italic>\n                    can activate macrophages in a manner that allows for increased\n                    <jats:italic>S. gordonii<\/jats:italic>\n                    survival and IL-1\u03b2 production above levels when\n                    <jats:italic>P. gingivalis<\/jats:italic>\n                    interacts with macrophages alone. We also use the mouse ligature-induced periodontal disease model to test the importance of NLRP6 in disease development. We found mice lacking NLRP6 had significantly reduced bone loss, IL-1\u03b2, and neutrophil infiltration following disease induced by\n                    <jats:italic>P. gingivalis<\/jats:italic>\n                    when\n                    <jats:italic>S. gordonii<\/jats:italic>\n                    or other mouse commensals were present, but had no effect when\n                    <jats:italic>S. gordonii<\/jats:italic>\n                    was inoculated alone. This work thus reveals an additional important inflammasome activation mechanism by which oral keystone pathogens may stimulate periodontal disease progression.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1014574","type":"journal-article","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T18:02:20Z","timestamp":1789495340000},"page":"e1014574","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Polymicrobial-driven NLRP6 inflammasome regulates IL-1\u03b2 production and alveolar bone loss in a murine model of periodontitis"],"prefix":"10.1371","volume":"22","author":[{"given":"Sarah","family":"Metcalfe","sequence":"first","affiliation":[{"name":"School of Dental Medicine, University at Buffalo","place":["Buffalo, New York, United States of America"],"department":["Department of Oral Biology"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajendra P.","family":"Settem","sequence":"additional","affiliation":[{"name":"School of Dental Medicine, University at Buffalo","place":["Buffalo, New York, United States of America"],"department":["Department of Oral Biology"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edwin J.","family":"Ovalle","sequence":"additional","affiliation":[{"name":"School of Dental Medicine, University at Buffalo","place":["Buffalo, New York, United States of America"],"department":["Department of Oral Biology"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Panasiewicz","sequence":"additional","affiliation":[{"name":"School of Dental Medicine, University at Buffalo","place":["Buffalo, New York, United States of America"],"department":["Department of Oral Biology"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandro","family":"Escobar","sequence":"additional","affiliation":[{"name":"Universidad de Chile","place":["Santiago, Chile"],"department":["Institute for Research in Dental Sciences, Faculty of Dentistry"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8944-6612","authenticated-orcid":true,"given":"Jason G.","family":"Kay","sequence":"additional","affiliation":[{"name":"School of Dental Medicine, University at Buffalo","place":["Buffalo, New York, United States of America"],"department":["Department of Oral Biology"]},{"name":"Jacobs School of Medicine and Biomedical Sciences, University at Buffalo","place":["Buffalo, New York, United States of America"],"department":["Department of Microbiology and Immunology"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,9,15]]},"reference":[{"issue":"6","key":"ppat.1014574.ref001","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1016\/j.tim.2016.02.010","article-title":"Dancing with the Stars: How Choreographed Bacterial Interactions Dictate 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