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

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.

• Authors: Larissa Staurengo-Ferrari, Silvia C Trevelin, Victor Fattori, Daniele C Nascimento, Kalil A de Lima, Jacinta S Pelayo, Florêncio Figueiredo, Rubia Casagrande, Sandra Y Fukada, Mauro M Teixeira, Thiago M Cunha, Foo Y Liew, Rene D Oliveira, Paulo Louzada-Junior, Fernando Q Cunha, José C Alves-Filho, Waldiceu A Verri
• Journal: Frontiers in immunology (Front Immunol) Vol. 9 Pg. 962 ( 2018) ISSN: 1664-3224 [Print] Switzerland
• PMID: 29867945 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• IL1RL1 protein, human
• IL33 protein, human
• Il1rl1 protein, mouse
• Il33 protein, mouse
• Interleukin-1 Receptor-Like 1 Protein
• Interleukin-33
• Interferon-gamma

Topics

• Animals
• Arthritis, Infectious (immunology, microbiology)
• Female
• Humans
• Interferon-gamma (genetics, immunology)
• Interleukin-1 Receptor-Like 1 Protein (genetics)
• Interleukin-33 (immunology)
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Mice, Knockout
• Osteoarthritis, Knee (immunology)
• Staphylococcal Infections (immunology)
• Staphylococcus aureus
• Synovial Fluid (immunology)