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Atopic dermatitis is a chronic inflammatory skin disease that affects 15-30% of children and approximately 5% of adults in industrialized countries (1). Although the pathogenesis of atopic dermatitis is not fully understood, the disease is mediated by an abnormal immunoglobulin-E immune response in the setting of skin barrier dysfunction (2). Mast cells contribute to immunoglobulin-E-mediated allergic disorders including atopic dermatitis (3). Upon activation, mast cells release their membrane-bound cytosolic granules leading to the release of several molecules that are important in the pathogenesis of atopic dermatitis and host defence (4). More than 90% of patients with atopic dermatitis are colonized with Staphylococcus aureus in the lesional skin whereas most healthy individuals do not harbour the pathogen (5). Several staphylococcal exotoxins can act as superantigens and/or antigens in models of atopic dermatitis (6). However, the role of these staphylococcal exotoxins in disease pathogenesis remains unclear. Here we report that culture supernatants of S. aureus contain potent mast-cell degranulation activity. Biochemical analysis identified δ-toxin as the mast cell degranulation-inducing factor produced by S. aureus. Mast cell degranulation induced by δ-toxin depended on phosphoinositide 3-kinase and calcium ([Ca.sup.2+]) influx; however, unlike that mediated by immunoglobulin-E crosslinking, it did not require the spleen tyrosine kinase. In addition, immunoglobulin-E enhanced δ-toxin-induced mast cell degranulation in the absence of antigen. Furthermore, S.aureusisolates recovered from patients with atopic dermatitis produced large amounts of δ-toxin. Skin colonization with S. aureus, but not a mutant deficient in δ-toxin, promoted immunoglobulin-E and interleukin-4 production, as well as inflammatory skin disease. Furthermore, enhancement of immunoglobulin-E production and dermatitis by δ-toxin was abrogated in [Kit.sup.W-sh/W-sh] mast-cell-deficient mice and restored by mast cell reconstitution. These studies identify δ-toxin as a potent inducer of mast cell degranulation and suggest a mechanistic link between S. aureuscolonization and allergic skin disease., Because mast cells (MCs) may play a critical role in the pathogenesis of atopic dermatitis (3), we asked first whether S. aureus can release factors that induce MC degranulation. We [...]

The finding that protein A of Staphylococcus aureus diverts the immune response so that it ineffectively responds to other structures from the bacterium explains the failure of ongoing attempts to develop working S. aureus vaccines., ('Staphylococcus aureus is a global pathogen of great importance, causing thousands of deaths each year in the United States alone. The main problems with S. aureus infections are frequent resistance [...]