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Publication : RAGE Deficiency Impairs Bacterial Clearance in Murine Staphylococcal Sepsis, but Has No Significant Impact on Staphylococcal Septic Arthritis.

First Author  Mohammad M Year  2016
Journal  PLoS One Volume  11
Issue  12 Pages  e0167287
PubMed ID  27907047 Mgi Jnum  J:250849
Mgi Id  MGI:6100418 Doi  10.1371/journal.pone.0167287
Citation  Mohammad M, et al. (2016) RAGE Deficiency Impairs Bacterial Clearance in Murine Staphylococcal Sepsis, but Has No Significant Impact on Staphylococcal Septic Arthritis. PLoS One 11(12):e0167287
abstractText  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.
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