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...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.展开更多
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。
文摘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.
