Caspase-11 mediated inflammasome activation in macrophages by systemic infection of A.actinomycetemcomitans exacerbates arthritis  

作　　者：Tokuju Okano Hiroshi Ashida Noriko Komatsu Masayuki Tsukasaki Tamako Iida Marie Iwasawa Yuto Takahashi Yasuo Takeuchi Takanori Iwata Miwa Sasai Masahiro Yamamoto Hiroshi Takayanagi Toshihiko Suzuki 

机构地区：[1]Department of Bacterial Pathogenesis,Infection and Host Response,Graduate School of Medical and Dental Sciences,Tokyo Medical and Dental University,Tokyo,Japan [2]Department of Immunology,Graduate School of Medicine and Faculty of Medicine,The University of Tokyo,Tokyo,Japan [3]Department of Osteoimmunology,Graduate School of Medicine and Faculty of Medicine,The University of Tokyo,Tokyo,Japan [4]Department of Lifetime Oral Health Care Science,Graduate School of Medical and Dental Sciences,Tokyo Medical and Dental University,Tokyo,Japan [5]Department of Periodontology,Graduate School of Medical and Dental Sciences,Tokyo Medical and Dental University,Tokyo,Japan [6]Department of Immunoparasitology,Research Institute for Microbial Diseases,Osaka University,Osaka,Japan

出　　处：《International Journal of Oral Science》2024年第3期499-514,共16页国际口腔科学杂志（英文版）

基　　金：supported by the Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science(15H04730,16H05186,16K08772,17K12004,19H03467,21J00572);a contract research fund from the Japan Program for Infectious Diseases Research and Infrastructure for research on emerging and re-emerging infectious diseases provided by the Japan Agency for Medical Research and Development(AMED);the Project for Promoting Leading-edge Research in Oral Science at Tokyo Medical and Dental University。

摘　　要：Clinical studies have shown that Aggregatibacter actinomycetemcomitans(A.actinomycetemcomitans)is associated with aggressive periodontitis and can potentially trigger or exacerbate rheumatoid arthritis(RA).However,the mechanism is poorly understood.Here,we show that systemic infection with A.actinomycetemcomitans triggers the progression of arthritis in mice anti-collagen antibody-induced arthritis(CAIA)model following IL-1βsecretion and cell infiltration in paws in a manner that is dependent on caspase-11-mediated inflammasome activation in macrophages.The administration of polymyxin B(PMB),chloroquine,and anti-CD11b antibody suppressed inflammasome activation in macrophages and arthritis in mice,suggesting that the recognition of lipopolysaccharide(LPS)in the cytosol after bacterial degradation by lysosomes and invasion via CD11b are needed to trigger arthritis following inflammasome activation in macrophages.These data reveal that the inhibition of caspase-11-mediated inflammasome activation potentiates aggravation of RA induced by infection with A.actinomycetemcomitans.This work highlights how RA can be progressed by inflammasome activation as a result of periodontitis-associated bacterial infection and discusses the mechanism of inflammasome activation in response to infection with A.actinomycetemcomitans.

关 键 词：CD11B inflam INFECTION 

分 类 号：R781.42[医药卫生—口腔医学] R593.22[医药卫生—临床医学]