Fibroblasts resist <i>Staphylococcus aureus</i> on the skin surface by responding to interleukin-1 and recruiting neutrophils.

Abstract

<i>Staphylococcus aureus</i> can cause serious infections, yet it can also reside on the skin without causing disease. This apparent paradox implies a strong host defense system, which prevents <i>S. aureus</i> from invading the dermis. In this study, we investigate how the skin detects and responds to superficial <i>S. aureus</i> exposure. Using unbiased transcriptomic, biochemical, and phosphoproteomic analyses, followed by targeted validation in human and mouse models, we found that fibroblast recognition of interleukin-1 is essential for immune response. Deletion or blockade of the interleukin-1 receptor type 1 (IL-1R1) in fibroblasts in vitro abolished keratinocyte-driven changes in gene expression and reduced chemokine production. Furthermore, the skin of mice lacking fibroblast IL-1R1 had fewer neutrophils and higher bacterial load after topical <i>S. aureus</i> application. These findings show that fibroblasts actively participate in innate immunity and highlight an IL-1R1-dependent keratinocyte-fibroblast-neutrophil axis of communication. Understanding this pathway provides insights into mechanisms that initiate neutrophil recruitment to the skin and may help develop new approaches to therapy.