{"title":"A complex of NLRP3 with caspase-4 is essential for inflammasome activation by Tannerella forsythia infection.","authors":"Chen Wei Hsu, Tokuju Okano, Yuiko Niinuma, Anongwee Leewananthawet, Tamako Iida, Poramed Onsoi, Kotchakorn Boonyaleka, Hiroshi Ashida, Toshihiko Suzuki","doi":"10.1093/intimm/dxae071","DOIUrl":null,"url":null,"abstract":"<p><p>Periodontitis, a chronic inflammatory disease of periodontal tissue, is often associated with a group of pathogenic bacteria known as the \"red complex,\" including Tannerella forsythia (T. forsythia). Previous papers showed that T. forsythia induces many kinds of inflammatory cytokines including IL-1β regulated by inflammasome activation. However, the physiological function for periodontitis and mechanism to induce inflammasome activation by T. forsythia infection are poorly understood. In this study, we demonstrate that NLRP3 and caspase-4 are essential for inflammasome activation by T. forsythia infection, playing a crucial role in IL-1β maturation in THP-1 cells. We also showed that knockout of ASC or GSDMD suppress the 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 (ROS) 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.</p>","PeriodicalId":13743,"journal":{"name":"International immunology","volume":" ","pages":""},"PeriodicalIF":4.8000,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"International immunology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1093/intimm/dxae071","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Periodontitis, a chronic inflammatory disease of periodontal tissue, is often associated with a group of pathogenic bacteria known as the "red complex," including Tannerella forsythia (T. forsythia). Previous papers showed that T. forsythia induces many kinds of inflammatory cytokines including IL-1β regulated by inflammasome activation. However, the physiological function for periodontitis and mechanism to induce inflammasome activation by T. forsythia infection are poorly understood. In this study, we demonstrate that NLRP3 and caspase-4 are essential for inflammasome activation by T. forsythia infection, playing a crucial role in IL-1β maturation in THP-1 cells. We also showed that knockout of ASC or GSDMD suppress the 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 (ROS) 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.
期刊介绍:
International Immunology is an online only (from Jan 2018) journal that publishes basic research and clinical studies from all areas of immunology and includes research conducted in laboratories throughout the world.