Mycobacterium tuberculosis promotes arthritis development through Toll-like receptor 2

J Bone Miner Metab. 2015 Mar;33(2):135-41. doi: 10.1007/s00774-014-0575-9. Epub 2014 Mar 15.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arthritis, Rheumatoid / metabolism
  • Arthritis, Rheumatoid / mortality*
  • Arthritis, Rheumatoid / pathology*
  • Cells, Cultured
  • Inflammation / metabolism
  • Interleukin-6 / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • Mycobacterium tuberculosis / physiology*
  • Toll-Like Receptor 2 / metabolism*
  • Tuberculosis / metabolism
  • Tuberculosis / microbiology*
  • Tuberculosis / pathology*


  • Interleukin-6
  • Tlr2 protein, mouse
  • Toll-Like Receptor 2