Exploring the Role of Staphylococcus Aureus Toxins in Atopic Dermatitis

Abstract

Atopic dermatitis (AD) is a chronic and inflammatory skin disease with intense pruritus and xerosis. AD pathogenesis is multifactorial, involving genetic, environmental, and immunological factors, including the participation of Staphylococcus aureus. This bacterium colonizes up to 30-100% of AD skin and its virulence factors are responsible for its pathogenicity and antimicrobial survival. This is a concise review of S. aureus superantigen-activated signaling pathways, highlighting their involvement in AD pathogenesis, with an emphasis on skin barrier disruption, innate and adaptive immunity dysfunction, and microbiome alterations. A better understanding of the combined mechanisms of AD pathogenesis may enhance the development of future targeted therapies for this complex disease.

Keywords: Staphylococcus aureus; adaptive immunity; atopic dermatitis; enterotoxins; innate immunity; microbiome.

Figure 1

(A) Staphylococcus aureus main compounds that contribute to enhanced bacterial virulence factor. SE—staphylococcal enterotoxins; TSST-1—toxic shock syndrome toxin-1. (B) S. aureus as a superantigen: direct binding to the major histocompatibility complex (MHC) class II molecule, with specificity for the T-cell receptor (TCR)-Vβ chain.

Figure 2

Superantigen-activated dendritic cells stimulate T helper (Th)2 cells to produce IL-4, IL-5, IL-13, and IL-31, leading to skin barrier disruption, decreased antimicrobial peptide production, impaired keratinocyte differentiation, and pruritus. In chronic atopic dermatitis (AD), there is an enrollment of Th1, Th22, and Th17 subsets that leads to epidermal thickening and abnormal keratinocyte proliferation (lichenification). Effects of staphylococcal enterotoxins in AD: 1. Dysfunctional CD4⁺ IL-22-secreting T cells and upregulated Tc22 cells. 2. Reduced peripheral blood mononuclear cell (PBMC) proliferative response corroborating an exhausted immune profile. 3. Increased frequency of CCR3⁺ and decreased expression of CD23 and CD62L receptors, and TIMP-1, TIMP-2, and CCL5 in purified eosinophils of AD patients even in a nonstimulated condition, indicating a potential breakdown in the tissue remodeling process in AD mediated by eosinophils. 4. Enhanced frequency of IL-10 under TLR4 and decreased frequency of IFN-γ and TNF under TLR2 and 7/8 stimulation in classic mDC (myeloid dendritic cells), indicating a tolerogenic profile in AD. All these findings together corroborate the chronic activated profile related to superantigens in AD pathogenesis.