title: RAGE Deficiency Impairs Bacterial Clearance in Murine Staphylococcal Sepsis, but Has No Significant Impact on Staphylococcal Septic Arthritis.
abstract: BACKGROUND
  Septic arthritis is a serious joint disease often caused by Staphylococcus aureus (S. aureus). Receptor for Advanced Glycation End products (RAGE) has an important role in several infections. We sought to investigate the role of RAGE in staphylococcal septic arthritis and sepsis in mice.
  
  
  METHODS
  Wild-type (WT) and RAGE deficient (RAGE-/-) mice were intra-articularly or intravenously inoculated with an arthritic or septic dose of S. aureus LS-1 strain. Clinical arthritis, weight development and mortality were monitored for 14 days. Serum levels of cytokines, kidney bacterial loads as well as micro-CT and histopathology of the joints were assessed.
  
  
  RESULTS
  RAGE-/- mice with septic arthritis had significantly lower IL-17A and higher bone mineral density (BMD) compared to the control group. However, no significant differences between the groups were observed regarding the weight loss, the severity and frequency of arthritis, and bacterial loads in the kidneys. In mice with sepsis, the overall mortality rate was similar in RAGE-/- (39%) and in WT mice (45%). However, RAGE-/- mice with sepsis had significantly higher bacterial load in their kidneys compared to the WT controls. In line with data from hematogenous S. aureus arthritis, RAGE deficiency had no impact on arthritis severity in local joint infection.
  
  
  CONCLUSIONS
  Our results indicate that lack of RAGE has no significant impact on septic arthritis. However, RAGE-/- mice had significantly higher BMD compared to WT mice, which coincided with lower IL-17A in RAGE-/- mice. In sepsis, RAGE deficiency impairs bacterial kidney clearance.
authors.affiliation: Department of Rheumatology and Inflammation Research, Institute of Medicine, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
authors.forename: Majd
authors.initials: M
authors.lastname: Mohammad
authors.affiliation: Department of Rheumatology and Inflammation Research, Institute of Medicine, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
authors.forename: Manli
authors.initials: M
authors.lastname: Na
authors.affiliation: Department of Rheumatology and Inflammation Research, Institute of Medicine, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
authors.forename: Amanda
authors.initials: A
authors.lastname: Welin
authors.affiliation: Department of Rheumatology and Inflammation Research, Institute of Medicine, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
authors.forename: Mattias N D
authors.initials: MN
authors.lastname: Svensson
authors.affiliation: Department of Rheumatology and Inflammation Research, Institute of Medicine, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
authors.forename: Abukar
authors.initials: A
authors.lastname: Ali
authors.affiliation: Department of Rheumatology and Inflammation Research, Institute of Medicine, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
authors.forename: Tao
authors.initials: T
authors.lastname: Jin
authors.affiliation: Department of Rheumatology and Inflammation Research, Institute of Medicine, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
authors.forename: Rille
authors.initials: R
authors.lastname: Pullerits
mesh_terms: D000818:Animals; D001170:Arthritis, Infectious / Q000097:blood / Q000175:diagnosis / Q000235:genetics* / Q000382:microbiology*; D058491:Bacterial Load; D015415:Biomarkers; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D005260:Female; D018836:Inflammation Mediators / Q000097:blood; D007719:Knee Joint / Q000000981:diagnostic imaging / Q000382:microbiology / Q000473:pathology; D008213:Lymphocyte Activation / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D000067759:Receptor for Advanced Glycation End Products / Q000172:deficiency*; D018805:Sepsis / Q000097:blood / Q000175:diagnosis / Q000235:genetics* / Q000382:microbiology*; D012720:Severity of Illness Index; D013203:Staphylococcal Infections / Q000097:blood / Q000175:diagnosis / Q000235:genetics* / Q000382:microbiology*; D055114:X-Ray Microtomography
chemical_list: D015415:Biomarkers; D016207:Cytokines; D018836:Inflammation Mediators; D000067759:Receptor for Advanced Glycation End Products