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Previous papers showed that T. forsythia induces many kinds of inflammatory cytokines including interleukin (IL)-1\u03b2 regulated by inflammasome activation. However, the physiological function of periodontitis and the mechanism to induce inflammasome activation by T. forsythia infection are poorly understood. In this study, we demonstrate that the Nod-like receptor pyrin domain containing 3 (NLRP3) and caspase-4 are essential for inflammasome activation by T. forsythia infection, playing a crucial role in IL-1\u03b2 maturation in THP-1 cells. We also showed that the knockout of ASC or Gasdermin D suppresses pyroptotic cell death. Moreover, co-immunoprecipitation assays confirmed the formation of a complex involving caspase-4, NLRP3, and ASC following T. forsythia infection. Additionally, reactive oxygen species production was identified as a key factor in caspase-4-mediated NLRP3 inflammasome activation by T. forsythia infection. These results enhance our understanding of inflammasome activation in response to T. forsythia infection and provide new insights into the pathogenic mechanisms of periodontitis.<\/jats:p>","DOI":"10.1093\/intimm\/dxae071","type":"journal-article","created":{"date-parts":[[2024,12,14]],"date-time":"2024-12-14T13:20:43Z","timestamp":1734182443000},"page":"261-271","source":"Crossref","is-referenced-by-count":2,"title":["A complex of NLRP3 with caspase-4 is essential for inflammasome activation by <i>Tannerella forsythia<\/i> infection"],"prefix":"10.1093","volume":"37","author":[{"given":"Chen-Wei","family":"Hsu","sequence":"first","affiliation":[{"name":"Department of Bacterial Pathogenesis, Infection and Host Response, Graduate School of Medical and Dental Sciences, Institute of SCIENCE TOKYO , Tokyo ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7179-6419","authenticated-orcid":false,"given":"Tokuju","family":"Okano","sequence":"additional","affiliation":[{"name":"Department of Bacterial Pathogenesis, Infection and Host Response, Graduate School of Medical and Dental Sciences, Institute of SCIENCE TOKYO , Tokyo ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuiko","family":"Niinuma","sequence":"additional","affiliation":[{"name":"Department of Bacterial Pathogenesis, Infection and Host Response, Graduate School of Medical and Dental Sciences, Institute of SCIENCE TOKYO , Tokyo ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anongwee","family":"Leewananthawet","sequence":"additional","affiliation":[{"name":"Specialized Dental Center, Department of Restorative Dentistry and Periodontology, Faculty of Dentistry, Chiang Mai University , Chiang Mai ,","place":["Thailand"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamako","family":"Iida","sequence":"additional","affiliation":[{"name":"Department of Bacterial Pathogenesis, Infection and Host Response, Graduate School of Medical and Dental Sciences, Institute of SCIENCE TOKYO , Tokyo ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Poramed","family":"Onsoi","sequence":"additional","affiliation":[{"name":"Department of Bacterial Pathogenesis, Infection and Host Response, Graduate School of Medical and Dental Sciences, Institute of SCIENCE TOKYO , Tokyo ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kotchakorn","family":"Boonyaleka","sequence":"additional","affiliation":[{"name":"Division of Periodontology, Department of Restorative Dentistry and Periodontology, Faculty of Dentistry, Chiang Mai University , Chiang Mai ,","place":["Thailand"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Ashida","sequence":"additional","affiliation":[{"name":"Department of Bacterial Pathogenesis, Infection and Host Response, Graduate School of Medical and Dental Sciences, Institute of SCIENCE TOKYO , Tokyo ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshihiko","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Bacterial Pathogenesis, Infection and Host Response, Graduate School of Medical and Dental Sciences, Institute of SCIENCE TOKYO , Tokyo ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,12,3]]},"reference":[{"key":"2025040805122595800_CIT0001","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1111\/j.1600-051X.1998.tb02419.x","article-title":"Microbial complexes in subgingival plaque","volume":"25","author":"Socransky","year":"1998","journal-title":"J Clin Periodontol"},{"key":"2025040805122595800_CIT0002","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1038\/nrmicro2337","article-title":"Periodontitis: a polymicrobial disruption of host homeostasis","volume":"8","author":"Darveau","year":"2010","journal-title":"Nat Rev Microbiol"},{"key":"2025040805122595800_CIT0003","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1038\/s41368-019-0064-z","article-title":"The cytokine network involved in the host immune response to periodontitis","volume":"11","author":"Pan","year":"2019","journal-title":"Int J Oral Sci"},{"key":"2025040805122595800_CIT0004","doi-asserted-by":"publisher","first-page":"e0242868","DOI":"10.1371\/journal.pone.0242868","article-title":"Periodontal pathogens alter the synovial proteome. 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