Staphylococcus aureus exacerbates dermal IL-33/ILC2 axis activation through evoking RIPK3/MLKL-mediated necroptosis of dry skin.
JCI Insight
; 9(6)2024 Feb 06.
Article
em En
| MEDLINE
| ID: mdl-38319737
ABSTRACT
Atopic dermatitis (AD) is a persistent skin disease typified by symptoms of dry skin and recurrent eczema. Patients with AD are at heightened risk for Staphylococcus aureus infection. Group 2 innate lymphoid cells (ILC2s) are mainly activated by epithelial cell-derived cytokines IL-33 and involved in the pathogenesis of AD. However, little is known about the effect of skin delipidization on the epithelial cell-derived cytokines and dermal ILC2s in AD. In our study, we investigated the mechanism by which S. aureus infection modulates and exacerbates the pathogenesis of dry skin, leading to type 2 inflammation in the context of innate immunity. In vivo, we found that S. aureus infection aggravated delipidization-induced dermal IL-33 release and dermal ILC2 accumulation, which exacerbated skin inflammation. We also noticed that Il33fl/fl K14cre mice and Tlr2-/- mice exhibited attenuated skin inflammation. In vitro, treatment with necroptosis inhibitors reduced IL-33 release from S. aureus-infected keratinocytes. Mechanistically, we observed an increase in the necroptosis-associated kinases, MLKL and RIPK3, in S. aureus-infected mice, indicating that IL-33 release was associated with necroptotic cell death responses. Our results reveal that S. aureus infection-elicited keratinocyte necroptosis contributes to IL-33-mediated type 2 inflammation, which exacerbates the pathogenesis of dry skin.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
6_ODS3_enfermedades_notrasmisibles
Base de dados:
MEDLINE
Assunto principal:
Infecções Estafilocócicas
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Dermatite Atópica
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Ictiose
Limite:
Animals
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Humans
Idioma:
En
Revista:
JCI Insight
Ano de publicação:
2024
Tipo de documento:
Article