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

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Staurengo-Ferrari, Larissa ^[1] ; Trevelin, Silvia C. ^{[2, 3]} ; Fattori, Victor ^[1] ; Nascimento, Daniele C. ^[2] ; de Lima, Kalil A. ^[2] ; Pelayo, Jacinta S. ^[4] ; Figueiredo, Florencio ^[5] ; Casagrande, Rubia ^[6] ; Fukada, Sandra Y. ^[7] ; Teixeira, Mauro M. ^[8] ; Cunha, Thiago M. ^[2] ; Liew, Foo Y. ^[9] ; Oliveira, Rene D. ^[10] ; Louzada-Junior, Paulo ^[10] ; Cunha, Fernando Q. ^[2] ; Alves-Filho, Jose C. ^[2] ; Verri, Waldiceu A. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Estadual Londrina, Ctr Ciencias Biol, Dept Patol, Londrina - Brazil

^[2] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Pharmacol, Ribeirao Preto - Brazil

^[3] Kings Coll London, British Heart Fdn Ctr, Cardiovasc Div, London - England

^[4] Univ Estadual Londrina, Ctr Ciencias Biol, Dept Microbiol, Londrina - Brazil

^[5] Univ Brasilia, Fac Med, Lab Pathol, Brasilia, DF - Brazil

^[6] Univ Estadual Londrina, Hlth Sci Ctr, Dept Pharmaceut Sci, Londrina - Brazil

^[7] Univ Sao Paulo, Sch Pharmaceut Sci Ribeirao Preto, Dept Phys & Chem, Ribeirao Preto - Brazil

^[8] Univ Fed Minas Gerais, Inst Ciencias Biol, Dept Bioquim & Imunol, Lab Imunofarmacol, Belo Horizonte, MG - Brazil

^[9] Univ Glasgow, Div Immunol Infect & Inflammat, Glasgow, Lanark - Scotland

^[10] Univ Sao Paulo, Sch Med Ribeirao Preto, Div Clin Immunol, Ribeirao Preto - Brazil

• Tipo de documento: Artigo Científico
• Fonte: FRONTIERS IN IMMUNOLOGY; v. 9, MAY 16 2018.
• Citações Web of Science: 3

Resumo

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. (AU)

• Processo FAPESP: 13/08216-2 - CPDI - Centro de Pesquisa em Doenças Inflamatórias
• Beneficiário: Fernando de Queiroz Cunha
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
• Processo FAPESP: 11/19670-0 - Mecanismos envolvidos na fisiopatologia da artrite reumatóide, dor e sepse
• Beneficiário: Fernando de Queiroz Cunha
• Modalidade de apoio: Auxílio à Pesquisa - Temático