Symbiotic microbiome Staphylococcus epidermidis restricts IL-33 production in allergic nasal epithelium via limiting the cellular necroptosis

Abstract

Abstract Background Allergic rhinitis (AR) is characterized by airway inflammation in nasal mucosa from inhaled allergens and interleukin (IL)-33 is the potent inducer of Th2 inflammation in allergic nasal epithelium. Staphylococcus epidermidis is one of the most abundant colonizers of the healthy human nasal mucosa and might impact the allergen-induced inflammatory responses in the nasal epithelium. Thus, we sought to characterize the mechanism of S. epidermidis regulating Th2 inflammation and IL-33 production in AR nasal mucosa. We isolated nasal commensal S. epidermidis from four healthy donors and determined the anti-allergic effect of S. epidermidis in normal human nasal epithelial (NHNE) and AR nasal epithelial (ARNE) cells and AR mice models. Results The AR symptoms were alleviated and eosinophilic infiltration, serum IgE levels, and Th2 cytokines were significantly decreased in OVA-sensitized AR mice in response to human nasal commensal S. epidermidis. The inoculation of S. epidermidis to NHNE cells reduced IL-33 and GATA3 transcriptions and also reduced IL-33 and GATA3 expression in ARNE cells and the nasal mucosa of AR mice. Our data exhibited that the cellular necroptosis of ARNE cells might be involved in IL-33 production and inoculation of S. epidermidis decreased the phosphorylation of necroptosis enzymes in ARNE cells, which was related to the reduction of IL-33 production. Conclusions Our findings indicate that human nasal commensal S. epidermidis reduces allergic inflammation by suppressing IL-33 production in nasal epithelium and blocking allergen-induced cellular necroptosis via S. epidermidis might be a key mechanism of reduction of IL-33 in allergic nasal epithelium.