IL-4 and IL-13 Produced During Allergic Skin Inflammation Exacerbate Mouse Model of Cutaneous Staphylococcus aureus Infection

Staphylococcus aureus (S. aureus) commonly colonizes the skin of patients with atopic dermatitis (AD) and its presence correlates with disease severity. The factors that promote colonization of AD skin with S. aureus are not fully understood. We investigated the potential reciprocal relationship between S. aureus skin infection and allergic skin inflammation. Il4-/-, Il13-/-, Il4-/-/Il13-/-mice and WT controls were epicutaneously (EC) sensitized with ovalbumin (OVA) or saline as control, and superficially infected with S. aureus. Cytokine mRNA expression was assessed by quantitative PCR, cell infiltrates were evaluated by flow cytometry, and bacterial burden was evaluated by counting colony-forming units in skin homogenates. OVA sensitized mouse skin exhibited increased S. aureus loads compared to saline sensitized skin. Superficial S. aureus application on OVA sensitized skin sites exaggerated infiltration by CD45+cells, CD4+T cells, eosinophils, basophils, ILCs and neutrophils. In addition, it enhanced Il4 and Il13 expression and decreased Il17a expression, but had no detectable effect on Ifng mRNA expression. Bacterial loads following S. aureus application to OVA sensitized skin were lower in Il4-/-,Il13-/- and Il4/Il13-/-mice compared to WT controls. Our results suggest a feed forward loop in which cutaneous S. aureus infection aggravates allergic skin inflammation and enhances the local type 2 responses, which in turn promote S. aureus growth and/or persistence.