The Pathogenetic Effect of Natural and Bacterial Toxins on Atopic Dermatitis

Abstract

Atopic dermatitis (AD) is a common allergic skin disease that is associated with chronic, recurrent eczematous and pruritic lesions at the flexural folds caused by interacting factors related to environmental and immune system changes. AD results in dry skin, and immunoglobulin E-mediated allergic reactions to foods and environmental allergens. While steroids and anti-histamines temporarily relieve the symptoms of AD, the possibility of side effects from pharmacological interventions remains. Despite intensive research, the underlying mechanisms for AD have not been clarified. A study of Staphylococcus aureus (S. aureus) established the role of its toxins in the pathogenesis of AD. Approximately 90% of patients with AD experience S. aureus colonization and up to 50%-60% of the colonizing S. aureus is toxin-producing. Any damage to the protective skin barrier allows for the entry of invading allergens and pathogens that further drive the pathogenesis of AD. Some natural toxins (or their components) that have therapeutic effects on AD have been studied. In addition, recent studies on inflammasomes as one component of the innate immune system have been carried out. Additionally, studies on the close relationship between the activation of inflammasomes and toxins in AD have been reported. This review highlights the literature that discusses the pathogenesis of AD, the role of toxins in AD, and the positive and negative effects of toxins on AD. Lastly, suggestions are made regarding the role of inflammasomes in AD.

Keywords: atopic dermatitis; pathogenesis; toxin.

Figure 1

Acute and chronic phases of atopic dermatitis (AD) [1]. In acute AD, allergens induce differentiation of Th2 cells and secretion of the pro-inflammatory cytokines such as interleukin 1 (IL-1), IL-6, and tumor necrosis factor (TNF)-α from dendritic cells (DCs). Damaged keratinocyte-derived thymic stromal lymphopoietin (TSLP) also derives DCs for polarization toward Th2 cells [31]. IL-4 and IL-13 suppress the induction of innate immune response genes and increase susceptibility to skin infections. The production of the Th1-like cytokines IL-12 and IL-18 induces the switch from Th2 cells to Th1 cells, and thereby leads to the chronic phase of AD [32]. The secretion of remodeling-associated cytokines such as transforming growth factor (TGF)-β1 and IL-11 [33], eosinophil recruitment, and IL-5 production contribute to the maintenance of chronic AD.

Figure 2

Mechanisms of S. aureus and its toxins on atopic dermatitis (AD). S. aureus and its toxins provide several mechanisms that result in AD. The S. aureus superantigens have the ability to induce cutaneous lymphocyte-associated antigen (CLA) expression as a skin-homing receptor on circulating T cells. Keratinocyte-derived chemokines and thymic stromal lymphopoietin (TSLP) induce the recruitment of T cells, Th2 cell differentiation, and the induction of T cells to secrete IL-5 and IL-31. The δ-toxin is an inducer of mast cell (MC) degranulation [125] and the α-toxin activates the nucleotide-binding oligomerization domain receptor protein 3 (NLRP3) inflammasome that eventually results in caspase-1 recruitment, and thereby leads to localized inflammatory responses via IL-1β and IL-18 secretion [126].