Interleukin-33 Receptor (ST2) Deficiency Improves the Outcome of Staphylococcus aureus-lnduced Septic Arthritis

The ST2 receptor is a member of the Toll/IL-1 R superfamily and interleukin-33 (IL-33) is its agonist Recently, it has been demonstrated that IL-33/ST2 axis plays key roles in inflammation and immune mediated diseases Here, we investigated the effect of ST2 deficiency in Staphylococcus auretus-induced septic arthritis physiopathology Synovial fluid samples from septic arthritis and osteoarthritis individuals were assessed regarding IL-33 and soluble (s) ST2 levels The IL-33 levels in samples from synovial fluid were significantly increased, whereas no sST2 levels were detected in patients with septic arthritis when compared with osteoarthritis individuals The intra-articular injection of 1 x 10(7) colony-forming unity/10 mu l of S. aureus American Type Culture Collection 6538 in wild-type (WT) mice induced IL-33 and sST2 production with a profile resembling the observation in the synovial fluid of septic arthritis patients Data using WT, and ST2 deficient ((-/-)) and interferon-gamma (IFN-gamma)(-/-) mice showed that ST2 deficiency shifts the immune balance toward a type 1 immune response that contributes to eliminating the infection due to enhanced microbicide effect via NO production by neutrophils and macrophages In fact, the treatment of ST2(-/-) bone marrow-derived macrophage cells with anti-IFN-gamma abrogates the beneficial phenotype in the absence of ST2, which confirms that ST2 deficiency leads to IFN-gamma expression and boosts the bacterial killing activity of macrophages against S. aureus In agreement, WT cells achieved similar immune response to ST2 deficiency by IFN-gamma treatment The present results unveil a previously unrecognized beneficial effect of ST2 deficiency in S. aureus-induced septic arthritis.