The chronic inflammatory skin disease atopic dermatitis (AD) is characterized by a dysbiosis of the microbiota. This is reflected by a decreased microbial diversity and the abundance of specific potential pathogenic strains such as Staphylococcus (S.) aureus. Staphylococcus (S.) epidermidis is an abundant member of the cutaneous microbiota and is considered generally as an apathogenic commensal that exhibits beneficial effects in AD, e.g. by controlling the growth of S. aureus. However, S. epidermidis is also frequently present in skin lesions of AD patients and a correlation between abundance of S. epidermidis and severity of AD has been reported. We therefore hypothesized that S. epidermidis may exhibit proinflammatory activities. To evaluate this hypothesis we stimulated cultured human keratinocytes and 3D skin models with different S. epidermidis isolates derived either from healthy skin or from lesional skin of AD patients. Real-time PCR and ELISA analyses revealed a significant induced expression of the AD-relevant cytokine thymic stromal lymphopoietin (TSLP) in keratinocytes and 3D skin after stimulation with S. epidermidis strains. S. epidermidis strains derived from lesional AD skin induced a higher TSLP expression than strains derived from healthy skin. Similar results were also obtained with the pro-inflammatory cytokines IL-17c and TNF-alpha. Both, S. epidermidis strains derived from healthy skin and strains derived from AD skin activated the inflammation-associated transcription factor NF-kappaB. Moreover, expression of the barrier-associated protein filaggrin was downregulated by S. epidermidis. Together, the observed S. epidermidis-mediated induction of proinflammatory mediators and downregulation of filaggrin in keratinocytes and 3D skin models may explain why AD patients carrying a high number of S. epidermidis are associated with a more severe inflamed disease state.

ESDR205 - The skin commensal Staphylococcus epidermidis induces inflammatory mediators in keratinocytes: Implications for atopic dermatitis

50th Annual Meeting of the European Society for Dermatological Research. VIRTUAL MEETING