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.
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.
Authors: Michelle Schultz; Majd Mohammad; Minh-Thu Nguyen; Zhicheng Hu; Anders Jarneborn; Carina M Wienken; Matti Froning; Rille Pullerits; Abukar Ali; Heiko Hayen; Friedrich Götz; Tao Jin Journal: Front Microbiol Date: 2022-03-09 Impact factor: 5.640
Authors: Abukar Ali; Manli Na; Mattias N D Svensson; Malin Magnusson; Amanda Welin; Jan-Christoph Schwarze; Majd Mohammad; Elisabet Josefsson; Rille Pullerits; Tao Jin Journal: PLoS One Date: 2015-07-02 Impact factor: 3.240
Authors: Majd Mohammad; Manli Na; Amanda Welin; Mattias N D Svensson; Abukar Ali; Tao Jin; Rille Pullerits Journal: PLoS One Date: 2016-12-01 Impact factor: 3.240
Authors: A Richter; J Listing; M Schneider; T Klopsch; A Kapelle; J Kaufmann; A Zink; A Strangfeld Journal: Ann Rheum Dis Date: 2015-11-13 Impact factor: 19.103