AUTHOR=Staurengo-Ferrari Larissa , Trevelin Silvia C. , Fattori Victor , Nascimento Daniele C. , de Lima Kalil A. , Pelayo Jacinta S. , Figueiredo Florêncio , Casagrande Rubia , Fukada Sandra Y. , Teixeira Mauro M. , Cunha Thiago M. , Liew Foo Y. , Oliveira Rene D. , Louzada-Junior Paulo , Cunha Fernando Q. , Alves-Filho José C. , Verri Waldiceu A. 

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

JOURNAL=Frontiers in Immunology

VOLUME=Volume 9 - 2018

YEAR=2018

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2018.00962

DOI=10.3389/fimmu.2018.00962

ISSN=1664-3224

ABSTRACT=The ST2 receptor is a member of the Toll/IL-1R superfamily and 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 aureus-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 1x107 CFU/10 microliters of S. aureus ATCC 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 IFN-gamma-/- mice showed that ST2 deficiency shifts the immune balance towards 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-/- BMDM 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 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.