Interleukin-33 receptor (ST2) deficiency improves the outcome of Staphylococcus aureus-induced septic arthritis

Staurengo-Ferrari, L. et al. (2018) Interleukin-33 receptor (ST2) deficiency improves the outcome of Staphylococcus aureus-induced septic arthritis. Frontiers in Immunology, 9, (doi: 10.3389/fimmu.2018.00962) (PMID:29867945) (PMCID:PMC5968393)

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Abstract

The ST2 receptor is a member of the Toll/IL-1R 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 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 1 × 107 colony-forming unity/10 μl 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-γ (IFN-γ)−/− 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-γ abrogates the beneficial phenotype in the absence of ST2, which confirms that ST2 deficiency leads to IFN-γ 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-γ treatment. The present results unveil a previously unrecognized beneficial effect of ST2 deficiency in S. aureus-induced septic arthritis.

Item Type:Articles
Additional Information:Funding: This work was supported by grants from CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico); MCTI/SETI/Fundação Araucária (Ministério da Ciência, Tecnologia e Inovação/Secretaria da Ciência, Tecnologia, e Ensino Superior do Paraná/Fundação Araucária); PPSUS grant from Decit/SCTIE/MS (Departamento de Ciência e Tecnologia da Secretaria de Ciência, Tecnologia e Insumos Estratégicos, Ministério da Saúde) intermediated by CNPq and support of Fundação Araucári; Coordenadoria de Aperfeiçoamento de Pessoal de Nível Superior (CAPES); INCT (National Institutes of Science and Technology)—MCTI/CNPq/CAPES/Fundação Araucária; São Paulo Research Foundation under grant agreements 2011/19670-0 (Thematic Project) and 2013/08216-2 (Center for Research in Inflammatory Disease); Financiadora de Estudos e Projetos and Secretaria de Estado da Ciência, Tecnologia e Ensino Superior do Paraná (FINEP/SETI-PR) and Central Multiusuária de Laboratórios de Pesquisa da UEL (CMLP). LS-F received a postdoctoral fellowship from CAPES.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Liew, Prof Foo
Authors: Staurengo-Ferrari, L., Trevelin, S. C., Fattori, V., Nascimento, D. C., de Lima, K. A., Pelayo, J. S., Figueiredo, F., Casagrande, R., Fukada, S. Y., Teixeira, M. M., Cunha, T. M., Liew, F. Y., Oliveira, R. D., Louzada-Junior, P., Cunha, F. Q., Alves-Filho, J. C., and Verri, W. A.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Frontiers in Immunology
Publisher:Frontiers Media
ISSN:1664-3224
ISSN (Online):1664-3224
Published Online:16 May 2018
Copyright Holders:Copyright © 2018 Staurengo-Ferrari, Trevelin, Fattori, Nascimento, de Lima, Pelayo, Figueiredo, Casagrande, Fukada, Teixeira, Cunha, Liew, Oliveira, Louzada-Junior, Cunha, Alves-Filho and Verri.
First Published:First published in Frontiers in Immunology
Publisher Policy:Reproduced under a Creative Commons license

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