Department of Bacterial Pathogenesis, Infection and Host Response, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
Department of Immunology, Graduate School of Medicine and Faculty of Medicine, The University of Tokyo, Tokyo, Japan.
Int J Oral Sci. 2024 Aug 15;16(1):54. doi: 10.1038/s41368-024-00315-x.
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，伴放线放线杆菌（Aggregatibacter actinomycetemcomitans，A. actinomycetemcomitans）与侵袭性牙周炎有关，并可能引发或加重类风湿关节炎（rheumatoid arthritis，RA）。然而，其机制尚不清楚。在这里，我们发现系统性感染伴放线放线杆菌会引发关节炎的进展，在白细胞介素-1β（IL-1β）分泌和爪细胞浸润后，在抗胶原蛋白抗体诱导关节炎（anti-collagen antibody-induced arthritis，CAIA）模型的小鼠中，这一过程依赖于巨噬细胞中 caspase-11 介导的炎症小体激活。多黏菌素 B（polymyxin B，PMB）、氯喹和抗 CD11b 抗体的给药抑制了巨噬细胞中的炎症小体激活和小鼠的关节炎，这表明在溶酶体降解细菌后细胞质中内毒素（lipopolysaccharide，LPS）的识别以及通过 CD11b 的入侵是触发炎症小体激活后引发关节炎所必需的。这些数据表明，抑制 caspase-11 介导的炎症小体激活可增强伴放线放线杆菌感染引发的 RA 恶化。这项工作强调了 RA 如何通过与牙周病相关的细菌感染引起的炎症小体激活而进展，并讨论了针对伴放线放线杆菌感染的炎症小体激活的机制。
