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Fibroblasts resist Staphylococcus aureus on the skin surface by responding to interleukin-1 and recruiting neutrophils

ABSTRACT: Staphylococcus aureus (SA) can cause serious infections, yet it often resides on the skin without causing disease. This apparent paradox suggests a strong host defense system which prevents SA from invading the dermis. In this study, we investigate how the skin detects and responds to superficial SA exposure. Using unbiased transcriptomic, biochemical, and phosphoproteomic analyses, followed by validation of the identified activation pathways in human and mouse models, we discovered that fibroblast recognition of interleukin-1 is essential for skin inflammation in response to topical SA. Deletion or blockade of the interleukin-1 receptor in fibroblasts in vitro abolished the change in gene expression and reduced chemokine production. Furthermore, PdgfraΔIl1r1mice that lack interleukin-1 receptor 1 only on fibroblasts decreased neutrophil infiltration and allowed increased bacterial growth on the surface of mouse skin after topical SA application. These findings show fibroblasts actively participate in innate immunity and highlight an interleukin-1-dependent communication pathway from keratinocytes to fibroblasts to neutrophils. Understanding this pathway provides new insights into mechanisms that initiate neutrophil recruitment to the skin and may help develop new approaches to therapy.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE311920 | GEO | 2026/06/29

REPOSITORIES: GEO

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