By SPC News Staff
Clinical studies have shown that periodontal disease with Aggregatibacter actinomycetemcomitans can exacerbate symptoms of rheumatoid arthritis (RA), but the molecular mechanisms behind this are unclear.
However, the inflammatory effects of periodontal bacteria can go well beyond the mouth, leading to systemic effects. Over the past few decades, clinical studies have revealed that the periodontal pathogen A. actinomycetemcomitans is related to the onset and worsening of RA. But how? Researchers from Tokyo Medical and Dental University conducted experiments to confirm whether A. actinomycetemcomitans infection influenced arthritis (Int J Oral Sci 2024;16[1]:54).
Using the collagen antibody-induced arthritis mouse model, which is a well-established experimental model that mimics several aspects of RA in humans, they found that infection with this specific bacterium led to increased limb swelling, cellular infiltration into the lining of the joints and higher levels of the inflammatory cytokine interleukin-1beta (IL-1beta) within the limbs.
Of note, these symptoms of worsening RA could be suppressed by administering a chemical agent called clodronate that depletes macrophages.
This demonstrated that macrophages were somehow involved in aggravating RA caused by A. actinomycetemcomitans infection.
Further investigation using macrophages derived from mouse bone marrow revealed that A. actinomycetemcomitans infection increased the production of IL-1beta. In turn, this triggered the activation of a multiprotein complex known as the inflammasome, which plays a key role in initiating and modulating the body’s inflammatory response to infections.
The researchers added yet one more piece to this puzzle using caspase-11-deficient mice.
In these animals, the activation of inflammasome, a multiprotein complex in the innate immune system that activates inflammatory responses and cell death, due to A. actinomycetemcomitans was suppressed.
Most importantly, caspase-11-deficient mice exhibited less deterioration of arthritis symptoms, hinting at the important role that caspase-11 plays in this context.
“Our research findings provide new insights into the link between periodontal pathogenic bacteria and the exacerbation of arthritis through [inflammatory] activation, offering important information on the long-debated relationship between periodontal disease and systemic diseases,” said Toshihiko Suzuki, DDS, PhD, one of the lead authors of the study. More study is needed to assure the effects also occur in people.
However, Dr. Suzuki said this research might contribute to new ways to treat or prevent RA, and be useful in the study of other autoimmune diseases.