{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T15:43:07Z","timestamp":1785771787983,"version":"3.56.0"},"reference-count":40,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,7,23]],"date-time":"2025-07-23T00:00:00Z","timestamp":1753228800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004608","name":"Natural Science Foundation of Jiangsu Province","doi-asserted-by":"publisher","award":["BK20231268"],"award-info":[{"award-number":["BK20231268"]}],"id":[{"id":"10.13039\/501100004608","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Oral Microbiology"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Tolerance refers to a hyporesponsiveness toward repeated stimulations with bacteria and their virulence factors, which might exist in the development of periodontitis. To identify the roles of tolerance induced by <jats:italic>Porphyromonas gingivalis<\/jats:italic> (<jats:italic>P. gingivalis<\/jats:italic>) in periodontitis, an original tolerized mice model was established by high\u2010dose of oral <jats:italic>P. gingivalis<\/jats:italic> inoculation following a primary infection. The alveolar bone loss of maxillae was detected by Micro\u2010CT. The infiltration of neutrophils and macrophages, and macrophage polarization were detected by IHC and flow cytometry, respectively. Residual <jats:italic>P. gingivalis<\/jats:italic> in subgingival plaque with and without macrophage\/neutrophil depletion was measured by real\u2010time PCR. Moreover, a real\u2010time PCR chip and bioinformatic analysis were then employed to explore the cytokine expression profiles in gingivae. The abundance of TNF\u2010\u03b1, Toll\u2010like receptor 2 (TLR2), and TLR4 were further verified by western blot. In comparison with the non\u2010tolerance group, TNF\u2010\u03b1 protein levels, alveolar bone loss, and the infiltration of neutrophils and macrophages in the tolerance group were significantly suppressed (<jats:italic>p<\/jats:italic> &lt; 0.05), while the quantities of residual <jats:italic>P. gingivalis<\/jats:italic> in subgingival plaque were increased (<jats:italic>p<\/jats:italic> &lt; 0.05). Moreover, the depletion of macrophages by liposomal clodronate weakened the inhibitory effect of tolerance, as evidenced by the lack of differences in the quantities of residual bacteria between the tolerance and non\u2010tolerance groups (<jats:italic>p<\/jats:italic> &gt; 0.05). Macrophages in gingivae of tolerized mice were more likely to polarize into M2 type. In addition, the expressions of cytokines related to neutrophil and macrophage infiltration and recruitment and the protein levels of TLR2 and TLR4 were decreased in tolerized mice (<jats:italic>p<\/jats:italic> &lt; 0.05). Tolerance induced by repeated <jats:italic>P. gingivalis<\/jats:italic> stimulations suppressed inflammatory responses in periodontal tissues, and the established periodontal tolerance model provided a reliable tool for the further study on periodontal tolerance in vivo.<\/jats:p>","DOI":"10.1111\/omi.70002","type":"journal-article","created":{"date-parts":[[2025,7,23]],"date-time":"2025-07-23T13:32:00Z","timestamp":1753277520000},"page":"223-233","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Tolerance Induced by <i>Porphyromonas gingivalis<\/i> Altered Inflammatory Responses in Mice"],"prefix":"10.1111","volume":"40","author":[{"given":"Miao","family":"Yu","sequence":"first","affiliation":[{"name":"Department of Periodontology The Affiliated Stomatological Hospital of Nanjing Medical University  Nanjing China"},{"name":"State Key Laboratory Cultivation Base of Research Prevention and Treatment for Oral Diseases  Nanjing China"},{"name":"Jiangsu Province Engineering Research Center of Stomatological Translational Medicine  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen\u2010bo","family":"Qian","sequence":"additional","affiliation":[{"name":"Department of Periodontology The Affiliated Stomatological Hospital of Nanjing Medical University  Nanjing China"},{"name":"State Key Laboratory Cultivation Base of Research Prevention and Treatment for Oral Diseases  Nanjing China"},{"name":"Jiangsu Province Engineering Research Center of Stomatological Translational Medicine  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan\u2010chun","family":"Fang","sequence":"additional","affiliation":[{"name":"Department of Periodontology The Affiliated Stomatological Hospital of Nanjing Medical University  Nanjing China"},{"name":"State Key Laboratory Cultivation Base of Research Prevention and Treatment for Oral Diseases  Nanjing China"},{"name":"Jiangsu Province Engineering Research Center of Stomatological Translational Medicine  Nanjing China"},{"name":"Department of Stomatology the Affiliated Suzhou Hospital of Nanjing University Medical School  Suzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Periodontology The Affiliated Stomatological Hospital of Nanjing Medical University  Nanjing China"},{"name":"State Key Laboratory Cultivation Base of Research Prevention and Treatment for Oral Diseases  Nanjing China"},{"name":"Jiangsu Province Engineering Research Center of Stomatological Translational Medicine  Nanjing China"},{"name":"Department of Stomatology Suzhou Municipal Hospital  Suzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiao","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Periodontology The Affiliated Stomatological Hospital of Nanjing Medical University  Nanjing China"},{"name":"State Key Laboratory Cultivation Base of Research Prevention and Treatment for Oral Diseases  Nanjing China"},{"name":"Jiangsu Province Engineering Research Center of Stomatological Translational Medicine  Nanjing China"},{"name":"Department of Stomatology Nanjing First Hospital  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Periodontology The Affiliated Stomatological Hospital of Nanjing Medical University  Nanjing China"},{"name":"State Key Laboratory Cultivation Base of Research Prevention and Treatment for Oral Diseases  Nanjing China"},{"name":"Jiangsu Province Engineering Research Center of Stomatological Translational Medicine  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,7,23]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.26919"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00229.2017"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2016.11.086"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2011-0392TR"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/iej.13957"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetimm.2012.05.012"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3671"},{"issue":"10","key":"e_1_2_10_9_1","article-title":"Constructing a Standard Curve for Real\u2010Time Polymerase Chain Reaction (PCR) Experiments","volume":"2018","author":"Green M. 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