Dissecting Keratinocyte Responses to Commensal and Pathogenic Staphylococcus Species Using a 3D Human Skin Model

Document Type

Article

Publication Date

2025

Keywords

JGM

Abstract

Staphylococcus aureus and Staphylococcus epidermidis are two common members of the skin microbiome. While S. aureus infection is associated with inflammatory skin disease and severe infection, and S. epidermidis is generally considered a commensal organism, little is known about how human skin cells distinguish between these species of contrasting pathogenic potential. Here, we use 3D skin models consisting of a layer of stratified keratinocytes grown on top of a fibroblast-embedded collagen matrix to show that barrier function-associated genes are differentially expressed upon stimulation with S. epidermidis versus S. aureus, as are two aryl-hydrocarbon receptor target genes, CYP1A1 and OVOL1. We also show that IL-1a expression and secretion is elevated upon stimulation with S. epidermidis, but not S. aureus. Overall, we provide preliminary evidence to suggest that host skin cells may differentially activate the proinflammatory response, increase the expression of proliferative keratin genes, and AhR target genes to distinguish between these two species.

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