title: Mycobacterium tuberculosis promotes arthritis development through Toll-like receptor 2.
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.
authors.affiliation: Department of Orthopaedic Surgery, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, Tokyo, 160-8582, Japan.
authors.forename: Hiroya
authors.initials: H
authors.lastname: Kanagawa
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Niki
authors.forename: Tami
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Yuiko
authors.initials: Y
authors.lastname: Sato
authors.forename: Eri
authors.initials: E
authors.lastname: Katsuyama
authors.forename: Atsuhiro
authors.initials: A
authors.lastname: Fujie
authors.forename: Wu
authors.initials: W
authors.lastname: Hao
authors.forename: Kana
authors.initials: K
authors.lastname: Miyamoto
authors.forename: Toshimi
authors.initials: T
authors.lastname: Tando
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Watanabe
authors.forename: Mayu
authors.initials: M
authors.lastname: Morita
authors.forename: Hideo
authors.initials: H
authors.lastname: Morioka
authors.forename: Morio
authors.initials: M
authors.lastname: Matsumoto
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Toyama
authors.forename: Takeshi
authors.initials: T
authors.lastname: Miyamoto
mesh_terms: D000818:Animals; D001172:Arthritis, Rheumatoid / Q000378:metabolism / Q000401:mortality* / Q000473:pathology*; D002478:Cells, Cultured; D007249:Inflammation / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009169:Mycobacterium tuberculosis / Q000502:physiology*; D051195:Toll-Like Receptor 2 / Q000378:metabolism*; D014376:Tuberculosis / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology*
chemical_list: D015850:Interleukin-6; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2