Study Finds Periodontal Pathogen Can Aggravate Rheumatoid Arthritis Symptoms
Research published in the International Journal of Oral Science has shown that periodontal disease with Aggregatibacter actinomycetemcomitans can exacerbate symptoms of rheumatoid arthritis (RA), but the molecular mechanisms behind this remain unclear.
In a recent study, researchers conducted several experiments in a mouse model of arthritis to shed light on this topic. Their findings reveal the crucial role of macrophages and the protein caspase-11 in this context, hinting at promising therapeutic targets for RA and other periodontal infection-related diseases.
Periodontal disease, which affects the gums and tissues that surround the teeth, is one of the most prevalent dental conditions worldwide. Most often caused by the formation and accumulation of bacterial biofilm around the teeth, periodontal disease can ultimately lead to tooth loss if left unattended.
Over the past few decades, clinical studies have revealed that the periodontal pathogen Aggregatibacter actinomycetemcomitans (A. actinomycetemcomitans) is closely related to the onset and worsening of rheumatoid arthritis (RA), a serious autoimmune disease that affects joints.
For the present study, the researchers conducted preliminary experiments to confirm whether A. actinomycetemcomitans infection influenced arthritis in mice.
To this end, they used 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-1β (IL-1β) within the limbs.
Notably, these symptoms of worsening RA could be suppressed by administering a chemical agent called clodronate that depletes macrophages -- a type of immune cell.
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-1β. 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, inflammasome activation 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 inflammasome activation, offering important information on the long-debated relationship between periodontal disease and systemic diseases," highlights Professor Toshihiko Suzuki, one of the lead authors of the study.
Reference: Tokuju Okano, Hiroshi Ashida, Noriko Komatsu, Masayuki Tsukasaki, Tamako Iida, Marie Iwasawa, Yuto Takahashi, Yasuo Takeuchi, Takanori Iwata, Miwa Sasai, Masahiro Yamamoto, Hiroshi Takayanagi, Toshihiko Suzuki. Caspase-11 mediated inflammasome activation in macrophages by systemic infection of A. actinomycetemcomitans exacerbates arthritis. International Journal of Oral Science, 2024; 16 (1) DOI: 10.1038/s41368-024-00315-x
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