Thymol attenuates the worsening of atopic dermatitis induced by Staphylococcus aureus membrane vesicles

Staphylococcus aureus membrane vesicles (MVs) aggravate atopic dermatitis (AD) through the delivery of bacterial effector molecules to host cells and the stimulation of inflammatory responses. This study investigated the inhibitory effect of thymol, a phenolic monoterpene found in essential oils derived from plants, on the worsening of AD induced by S. aureus MVs both in vitro and in vivo. The sub-minimal inhibitory concentrations of thymol disrupted S. aureus MVs. Intact S. aureus MVs induced the expression of pro-inflammatory cytokine (interleukin (IL)-1 beta, IL-6, and tumor necrosis factor-alpha) and chemokine (IL-8 and monocyte chemoattractant protein-1) genes in cultured keratinocytes, whereas thymol-treated S. aureus MVs did not stimulate the expression of these genes. Topical application of thymol-treated S. aureus MVs or treatment with thymol after intact S. aureus MVs to AD-like skin lesions diminished the pathology of AD. This included decreases in epidermal/dermal thickness and infiltration of eosinophils/mast cells, and inhibited expression of pro-inflammatory cytokine and chemokine genes in mouse AD model. Moreover, thymol significantly suppressed the Th1, Th2, and Th17-mediated inflammatory responses in AD-like skin lesions induced by S. aureus MVs, and reduced the serum levels of immunoglobulin (Ig) G2a, mite-specific IgE, and total IgE. In summary, thymol disrupts S. aureus MVs and suppresses inflammatory responses in AD-like skin lesions aggravated by S. aureus MVs. Our results suggest that thymol is a possible candidate for the management of AD aggravation induced by S. aureus colonization or infection in the lesions.