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Antibiotic‐Killed Staphylococcus aureus Induces Destructive Arthritis in Mice
Author(s) -
Ali Abukar,
Zhu Xuefeng,
Kwiecinski Jakub,
Gjertsson Inger,
Lindholm Catharina,
Iwakura Yoichiro,
Wang Xiaoyang,
Lycke Nils,
Josefsson Elisabet,
Pullerits Rille,
Jin Tao
Publication year - 2015
Publication title -
arthritis and rheumatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.106
H-Index - 314
eISSN - 2326-5205
pISSN - 2326-5191
DOI - 10.1002/art.38902
Subject(s) - synovitis , staphylococcus aureus , septic arthritis , medicine , inflammation , arthritis , antibiotics , immunology , cloxacillin , tumor necrosis factor alpha , microbiology and biotechnology , biology , bacteria , penicillin , genetics
Objective Permanent reduction in joint function is a severe postinfectious complication in patients with Staphylococcus aureus septic arthritis. We undertook this study to determine whether this reduction in joint function might be caused by persistent joint inflammation after the adequate eradication of bacteria by antibiotics. Methods After intraarticular injection of cloxacillin‐killed S aureus into mouse knee joints, we investigated whether antibiotic‐killed S aureus induced joint inflammation and elucidated the molecular and cellular mechanisms of this type of arthritis. Results Intraarticular injection of antibiotic‐killed S aureus induced mild‐to‐moderate synovitis and bone erosions that lasted for a minimum of 14 days. Compared with wild‐type animals, mice deficient in tumor necrosis factor receptor type I (TNFRI), receptor for advanced glycation end products (RAGE), or Toll‐like receptor 2 (TLR‐2) had a significantly reduced frequency and severity of synovitis. Combined depletion of monocytes and neutrophils also resulted in a significantly lower frequency of synovitis. Among bacterial factors, insoluble cell debris played a more important role than bacterial DNA or soluble components in inducing joint inflammation. Importantly, anti‐TNF therapy abrogated joint inflammation induced by antibiotic‐killed S aureus . Conclusion Antibiotic‐killed S aureus induced and maintained joint inflammation mediated through TLR‐2, TNFRI, and RAGE. The cross‐talk between neutrophils and monocytes is responsible for this type of arthritis. Anti‐TNF therapy might be used as a novel strategy, in combination with antibiotics, to treat staphylococcal septic arthritis.