title: Antibiotic-killed Staphylococcus aureus induces destructive arthritis in mice.
abstract: 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.
  
  
  CONCLUSIONS
  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.affiliation: Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
authors.forename: Abukar
authors.initials: A
authors.lastname: Ali
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Zhu
authors.forename: Jakub
authors.initials: J
authors.lastname: Kwiecinski
authors.forename: Inger
authors.initials: I
authors.lastname: Gjertsson
authors.forename: Catharina
authors.initials: C
authors.lastname: Lindholm
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Iwakura
authors.forename: Xiaoyang
authors.initials: X
authors.lastname: Wang
authors.forename: Nils
authors.initials: N
authors.lastname: Lycke
authors.forename: Elisabet
authors.initials: E
authors.lastname: Josefsson
authors.forename: Rille
authors.initials: R
authors.lastname: Pullerits
authors.forename: Tao
authors.initials: T
authors.lastname: Jin
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001169:Arthritis, Experimental / Q000378:metabolism* / Q000382:microbiology* / Q000473:pathology; D001170:Arthritis, Infectious / Q000378:metabolism* / Q000382:microbiology* / Q000473:pathology; D002450:Cell Communication / Q000502:physiology; D003023:Cloxacillin / Q000494:pharmacology*; D004195:Disease Models, Animal; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009000:Monocytes / Q000473:pathology; D009504:Neutrophils / Q000473:pathology; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D012720:Severity of Illness Index; D013211:Staphylococcus aureus / Q000187:drug effects*; D051195:Toll-Like Receptor 2 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D047888:Receptors, Tumor Necrosis Factor, Type I; C493486:Tlr2 protein, mouse; C506236:Tnfrsf1a protein, mouse; D051195:Toll-Like Receptor 2; D003023:Cloxacillin