Staphylococcus aureus proteases trigger eosinophil-mediated skin inflammation

Abstract

Staphylococcus aureus skin colonization and eosinophil infiltration are associated with many inflammatory skin disorders, including atopic dermatitis, bullous pemphigoid, Netherton’s syndrome, and prurigo nodularis. However, whether there is a relationship between S. aureus and eosinophils and how this interaction influences skin inflammation is largely undefined. We show in a preclinical mouse model that S. aureus epicutaneous exposure induced eosinophil-recruiting chemokines and eosinophil infiltration into the skin. Remarkably, we found that eosinophils had a comparable contribution to the skin inflammation as T cells, in a manner dependent on eosinophil-derived IL-17A and IL-17F production. Importantly, IL-36R signaling induced CCL7-mediated eosinophil recruitment to the inflamed skin. Last, S. aureus proteases induced IL-36α expression in keratinocytes, which promoted infiltration of IL-17-producing eosinophils. Collectively, we uncovered a mechanism for S. aureus proteases to trigger eosinophil-mediated skin inflammation, which has implications in the pathogenesis of inflammatory skin diseases.

The New Paradigm: The Role of Proteins and Triggers in the Evolution of Allergic Asthma

“…Recent evidence has demonstrated that, in the skin of a preclinical mouse model, eosinophilrecruiting chemokines (and eosinophil infiltration) are induced after Staphylococcus aureus epicutaneous exposure, the IL-36α-IL-36R pathway is involved [194].…”

The New Paradigm: The Role of Proteins and Triggers in the Evolution of Allergic Asthma

“…Recent evidence has demonstrated that, in the skin of a preclinical mouse model, eosinophil-recruiting chemokines (and eosinophil infiltration) are induced after Staphylococcus aureus epicutaneous exposure, and the IL-36α-IL-36R pathway is involved [ 194 ].…”