Innate host defense lysozyme may help control Staphylococcus aureus in atopic dermatitis
ABSTRACT Atopic dermatitis (AD) is a chronic pruritic skin condition characterized by lesions associated with colonization and infection by Staphylococcus aureus. There is growing evidence that S. aureus contributes to symptoms and persistence of AD through production of cytotoxins, superantigens, and proteases. When AD is treated with the interleukin-4 receptor blocking antibody, dupilumab, S. aureus colonization declines rapidly. Here, we examined the possible involvement of the host lysozyme-mediated innate immune response in helping to control S. aureus burden in AD patients. S. aureus is not killed by lysozyme, but the molecule inhibits S. aureus exotoxin and exoenzyme (exoprotein) production. Reduced S. aureus abundance during dupilumab treatment correlated positively with reduced lysozyme levels. S. aureus colonization and lysozyme levels were not altered in placebo-treated participants until they entered the open-label phase of the study (non-blinded phase) when all participants were treated with dupilumab. During that phase, the S. aureus and lysozyme levels declined. These findings suggest that AD patients may respond to cutaneous S. aureus colonization by upregulating lysozyme production. IMPORTANCE Staphylococcus aureus is increasingly viewed as an important contributor to atopic dermatitis (AD) persistence. The host responds to AD by producing cationic peptides, including lysozyme. Lysozyme cannot kill S. aureus, but the innate defense molecule downregulates exotoxin and exoenzyme production, limiting S. aureus-induced inflammation. Clinical improvement of AD likely requires balancing the inflammatory cascades induced by S. aureus versus host innate immunity. Staphylococcus aureus is increasingly viewed as an important contributor to atopic dermatitis (AD) persistence. The host responds to AD by producing cationic peptides, including lysozyme. Lysozyme cannot kill S. aureus, but the innate defense molecule downregulates exotoxin and exoenzyme production, limiting S. aureus-induced inflammation. Clinical improvement of AD likely requires balancing the inflammatory cascades induced by S. aureus versus host innate immunity.