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Mycobacterium tuberculosis promotes arthritis development through toll-like receptor 2

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Abstract

Rheumatoid arthritis (RA) is a multifactorial disease caused by genetic and environmental factors: however, precise molecular mechanisms underlying its pathogenesis remain largely unknown. Treatment of RA patients with disease-modifying biological agents occasionally promotes Mycobacterium tuberculosis infection or recurrence of M. tuberculosis, although how infection promotes arthritis has not been characterized. Here, we found that arthritis phenotypes in a collagen-induced mouse model were evident only when killed M. tuberculosis was co-administered. Treatment of cultured macrophages with killed M. tuberculosis promoted production of IL-6, a major inflammatory cytokine in RA patients, while similar treatment of TLR2-deficient macrophages failed to induce IL-6 expression. Arthritis scores, joint destruction, and serum IL-6 levels were all significantly ameliorated in TLR2-deficient compared with wild-type mice, even in animals treated with killed M. tuberculosis. These results suggest that M. tuberculosis infection enhances arthritis development and that TLR2 could serve as a therapeutic target for some forms of the disease.

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Abbreviations

RA:

Rheumatoid arthritis

TLRs:

Toll-like receptors

CIA:

Collagen-induced arthritis

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Acknowledgments

T. Miyamoto was supported by a Grant-in-Aid for Scientific Research, from the Takeda Science Foundation, Japan.

Conflict of interest

None.

Author information

Authors and Affiliations

  1. Department of Orthopaedic Surgery, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, Tokyo, 160-8582, Japan

    Hiroya Kanagawa, Yasuo Niki, Tami Kobayashi, Yuiko Sato, Eri Katsuyama, Atsuhiro Fujie, Wu Hao, Kana Miyamoto, Toshimi Tando, Ryuichi Watanabe, Hideo Morioka, Morio Matsumoto, Yoshiaki Toyama & Takeshi Miyamoto

  2. Department of Musculoskeletal Reconstruction and Regeneration Surgery, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, Tokyo, 160-8582, Japan

    Yuiko Sato

  3. Department of Dentistry and Oral Surgery, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, Tokyo, 160-8582, Japan

    Mayu Morita

  4. Department of Integrated Bone Metabolism and Immunology, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, Tokyo, 160-8582, Japan

    Takeshi Miyamoto

Authors
  1. Hiroya Kanagawa
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  2. Yasuo Niki
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  3. Tami Kobayashi
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  8. Kana Miyamoto
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  9. Toshimi Tando
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  12. Hideo Morioka
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  13. Morio Matsumoto
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  14. Yoshiaki Toyama
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  15. Takeshi Miyamoto
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Corresponding author

Correspondence to Takeshi Miyamoto.

Additional information

H. Kanagawa and Y. Niki contributed equally to this work.

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Kanagawa, H., Niki, Y., Kobayashi, T. et al. Mycobacterium tuberculosis promotes arthritis development through toll-like receptor 2. J Bone Miner Metab 33, 135–141 (2015). https://doi.org/10.1007/s00774-014-0575-9

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  • DOI: https://doi.org/10.1007/s00774-014-0575-9

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