Staphylococcal Alpha-Toxin Is a Strong Inducer of Interleukin-17 in Humans

Abstract

Patients with atopic dermatitis (AD) are frequently colonized with Staphylococcus aureus, with one-third of isolates producing alpha-toxin. Moreover, S. aureus colonization is positively correlated with the severity of eczema. Interleukin-17A (IL-17A) has gained attention in diseases associated with chronic skin infections. The aim of this study was to investigate the effects of sublytic alpha-toxin concentrations on IL-17A production. Sublytic alpha-toxin concentrations strongly induced IL-17A in peripheral blood mononuclear cells (PBMCs), isolated CD4 ؉ T cells, polarized Th17 cells, and Th17 clones from reactive atopy patch test lesions and blood from AD patients. Alphatoxin induced IL-17A directly in T cells. The effect of alpha-toxin was further amplified by upregulation of IL-1 in monocytes. In conclusion, higher levels of IL-17A secretion induced by alpha-toxin in the skin partially explain how colonization with S. aureus can contribute to chronic skin inflammation.Atopic dermatitis (AD) and psoriasis (PS) are the most common immune-mediated chronic inflammatory skin diseases, with an increasing prevalence, affecting approximately 1 to 4% of the population in industrial countries (8,36,39). One hallmark of AD is a striking susceptibility to colonization with Staphylococcus aureus: 80 to 100% of patients with AD are colonized with S. aureus (4, 27). In contrast, S. aureus can be isolated from the skin of only 5 to 30% of healthy individuals, mainly from intertriginous areas (27). Moreover, a positive correlation between disease severity and extent and S. aureus colonization of lesional and nonlesional skin has been noted (4), which may be due to IgE-mediated hypersensitivity (3, 23) or to production of exotoxins with superantigenic properties (28,40,46). For PS, one study detected S. aureus in nonlesional skin of 27% of patients and in 46% of skin lesions (26). Tomi et al. investigated 25 PS patients: the skin of 60% of patients was positive for S. aureus, and isolated S. aureus strains were toxigenic, carrying staphylococcal enterotoxins A to D (SEA to SED), in 36% of patients. Furthermore, the PASI score correlated significantly with the presence of enterotoxinproducing S. aureus strains (43).Recently, the superantigen SEB was shown to enhance house dust mite-induced patch test reactions in patients with AD (20). Besides unspecific stimulation of T-cell receptor (TCR) V␤ chains, superantigens can augment an antigen-specific T-helper 1 (Th1) response via the induction of interleukin-12 (IL-12) in antigen-presenting cells (APCs), which might contribute to AD becoming chronic (7,22). On the other hand, the severity of AD decreased in patients colonized with nontoxigenic S. aureus strains upon antimicrobial treatment as well, which suggests the involvement of pathogenic factors other than superantigens derived from S. aureus (5).A distinct percentage of S. aureus strains are able to produce alpha-toxin, a potent 33-kDa cytolysin which does not belong to the group of enterotoxins (superantigens) (9). In a for...

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Relationship Between Serum Interleukin-17F Level and Severity of Atopic Dermatitis in Children

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Host Response Signature to Staphylococcus aureus Alpha-Hemolysin Implicates Pulmonary Th17 Response

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