Staphylococcus aureus -toxin present on skin promotes the development of food allergy in a murine model

Background: Patients with food allergy often suffer from atopic dermatitis, in which Staphylococcus aureus colonization is frequently observed. Staphylococcus aureus delta-toxin activates mast cells and promotes T helper 2 type skin inflammation in the tape-stripped murine skin. However, the physiological effects of delta-toxin present on the steady-state skin remain unknown. We aimed to investigate whether delta-toxin present on the steady-state skin impacts the development of food allergy. Material and methods: The non-tape-stripped skins of wild-type, Kit(W-sh/W-sh), or ST2-deficient mice were treated with ovalbumin (OVA) with or without delta-toxin before intragastric administration of OVA. The frequency of diarrhea, numbers of jejunum or skin mast cells, and serum levels of OVA-specific IgE were measured. Conventional dendritic cell 2 (cDC2) in skin and lymph nodes (LN) were analyzed. The cytokine levels in the skin tissues or culture supernatants of delta-toxin-stimulated murine keratinocytes were measured. Anti-IL-1 alpha antibody-pretreated mice were analyzed. Results: Stimulation with delta-toxin induced the release of IL-1 alpha, but not IL-33, in murine keratinocytes. Epicutaneous treatment with OVA and delta-toxin induced the local production of IL-1 alpha. This treatment induced the translocation of OVA-loaded cDC2 from skin to draining LN and OVA-specific IgE production, independently of mast cells and ST2. This resulted in OVA-administered food allergic responses. In these models, pretreatment with anti-IL-1 alpha antibody inhibited the cDC2 activation and OVA-specific IgE production, thereby dampening food allergic responses. Conclusion: Even without tape stripping, delta-toxin present on skin enhances epicutaneous sensitization to food allergen in an IL-1 alpha-dependent manner, thereby promoting the development of food allergy.