AUTHOR=Yamada Hiromichi , Kaitani Ayako , Izawa Kumi , Ando Tomoaki , Kamei Anna , Uchida Shino , Maehara Akie , Kojima Mayuki , Yamamoto Risa , Wang Hexing , Nagamine Masakazu , Maeda Keiko , Uchida Koichiro , Nakano Nobuhiro , Ohtsuka Yoshikazu , Ogawa Hideoki , Okumura Ko , Shimizu Toshiaki , Kitaura Jiro 

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

JOURNAL=Frontiers in Immunology

VOLUME=Volume 14 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1173069

DOI=10.3389/fimmu.2023.1173069

ISSN=1664-3224

ABSTRACT=BACKGROUND: Patients with food allergy often suffer from atopic dermatitis, in which Staphylococcus aureus colonization is frequently observed. Staphylococcus aureus -toxin activates mast cells and promotes T helper 2 type skin inflammation in the tape-stripped murine skin. However, the physiological effects of -toxin present on the steady-state skin remain unknown. We aimed to investigate whether -toxin present on the steady-state skin impacts the development of food allergy.
MATERIAL AND METHODS: The non-tape-stripped skins of wild-type, KitW-sh/W-sh, or ST2-deficient mice were treated with ovalbumin (OVA) with or without -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 -toxin-stimulated murine keratinocytes were measured. Anti-IL-1 antibody-pretreated mice were analyzed.   
RESULTS: Stimulation with -toxin induced the release of IL-1, but not IL-33, in murine keratinocytes. Epicutaneous treatment with OVA and -toxin induced the local production of IL-1 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 antibody inhibited the cDC2 activation and OVA-specific IgE production, thereby dampening food allergic responses.
CONCLUSION: Even without tape stripping, -toxin present on skin enhances epicutaneous sensitization to food allergen in an IL-1-dependent manner, thereby promoting the development of food allergy.