Clinical research indicates that periodontal disease caused by Aggregatibacter actinomycetemcomitans can worsen rheumatoid arthritis (RA) symptoms, but the specific molecular mechanisms involved are not yet fully understood. A recent study aimed to clarify this relationship by performing various tests on a mouse model of arthritis. The results underscore the significant involvement of macrophages and the protein caspase-11 in this process, suggesting they could serve as valuable targets for potential RA therapies and other diseases related to periodontal infections.
Periodontal disease, impacting the gums and surrounding tissues of the teeth, is one of the most common dental issues globally. It usually arises from the buildup of bacterial biofilm on the teeth, which, if untreated, can eventually result in tooth loss. Interestingly, the inflammatory responses triggered by periodontal bacteria can extend beyond the oral cavity, having systemic implications. In recent years, studies have indicated that the periodontal pathogen Aggregatibacter actinomycetemcomitans (A. actinomycetemcomitans) is connected to the emergence and exacerbation of rheumatoid arthritis (RA), a severe autoimmune disorder affecting joints. However, the underlying molecular mechanisms remain largely uninvestigated.
A recent study published on 15 August 2024, in the International Journal of Oral Science, was conducted by a research team from Tokyo Medical and Dental University (TMDU) in Japan to address this knowledge deficiency through rigorous mechanistic research in an animal model.
The researchers first carried out preliminary experiments to determine if A. actinomycetemcomitans infection impacted arthritis in mice. They employed the collagen antibody-induced arthritis mouse model, a well-known experimental setup that replicates several features of RA in humans. Their findings indicated that infection with this specific bacterium resulted in increased swelling in the limbs, infiltration of cells into joint linings, and elevated levels of the inflammatory cytokine interleukin-1β (IL-1β) in the limbs.
Interestingly, the adverse effects on RA symptoms were lessened by administering a chemical called clodronate, which depletes macrophages — a type of immune cell. This finding suggested that macrophages played a role in exacerbating RA linked to A. actinomycetemcomitans infection.
Further analyses using macrophages isolated from mouse bone marrow showed that A. actinomycetemcomitans infection led to increased IL-1β production. This, in turn, activated a multiprotein complex referred to as the inflammasome, which is crucial for starting and regulating the body’s inflammatory response to infections.
Additional exploration with mice lacking caspase-11 revealed that inflammasome activation triggered by A. actinomycetemcomitans was inhibited. Crucially, these caspase-11-deficient mice showed less severe arthritic symptoms, highlighting the important role of caspase-11 in this scenario. “Our research findings offer fresh insights into the connection between periodontal pathogenic bacteria and the worsening of arthritis through inflammasome activation, providing valuable information on the long-discussed link between periodontal and systemic diseases,” says Professor Toshihiko Suzuki, a lead author of the study.
Hopefully, these findings will aid in creating new therapeutic approaches for managing RA. “The outcomes of this research could lead to breakthroughs in clinical treatments for RA triggered by infection with A. actinomycetemcomitans. We suggest that inhibiting inflammasome activation might reduce inflammation spread to the joints, leading to symptom relief in arthritis,” explains lead author Dr. Tokuju Okano. “Furthermore, our findings could contribute to treatment strategies not just for arthritis but also for other systemic diseases, such as Alzheimer’s disease, which is also linked to periodontal pathogenic bacteria,” he adds with optimism for the future.
