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-1β secretion 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.

临床研究表明， Aggregatibacter actinomycetemcomitans ( A. actinomycetemcomitans ) 与侵袭性牙周炎有关，并可能引发或加剧类风湿性关节炎 (RA)。然而，人们对该机制知之甚少。在这里，我们发现，在小鼠抗胶原抗体诱导的关节炎 (CAIA) 模型中，伴随 IL-1β 分泌和爪子细胞浸润， A. actinomycetemcomitans的全身感染会引发关节炎的进展，其方式依赖于 caspase-11-介导巨噬细胞中炎症小体的激活。给予多粘菌素 B (PMB)、氯喹和抗 CD11b 抗体可抑制小鼠巨噬细胞和关节炎中的炎症小体激活，这表明细菌被溶酶体降解并通过 CD11b 入侵后需要识别胞质溶胶中的脂多糖 (LPS)，从而抑制炎症反应。巨噬细胞中炎症小体激活后引发关节炎。这些数据表明，抑制 caspase-11 介导的炎性小体激活会加剧由伴放线放线菌感染引起的 RA 加重。这项工作重点介绍了牙周炎相关细菌感染导致的炎症小体激活如何导致 RA 进展，并讨论了炎症小体激活响应A感染的机制。伴放线菌。