Staphylococcus aureus (S. aureus) is one of the skin resident bacteria frequently isolated from the skin of atopic dermatitis (AD) patients. Many murine AD models suggest that S. aureus proliferation on the skin promote inflammation via bacterial penetration across disrupted skin barrier. Hence, it is commonly accepted that S. aureus is harmful to barrier disrupted skin. On the other hand, a recent birth cohort study has shown positive association between the S. aureus colonization and subsequent development of AD even without barrier disruption. This result suggests that skin colonized S. aureus may have some effect on healthy skin. However, the underlying mechanism remains unclear. To this end, we sought to investigate the effect of S. aureus colonization on healthy skin by using skin commensal association model in which S. aureus is topically applied to wild type murine ears. With this bacterial association, we could not find any clinical inflammation. Interestingly, S. aureus colonized skin showed slight infiltration of neutrophils in the epidermis together with inducing IL-1 mRNA expression compared to non-colonized control skin. Next, we evaluated the susceptibility of S. aureus colonized skin to inflammation by using phorbol myristate acetate (PMA)-induced irritant contact dermatitis (ICD) model. S. aureus colonized skin showed stronger ICD responses compared to the PMA applied skin without bacteria association i.e., increasement of ear swelling, massive infiltration of innate cells. Neutrophil depletion suppressed the exacerbated inflammation by S. aureus. Leukotriene B4 receptor blockade and IL-1β neutralization reduced the number of infiltrated neutrophils, and ameliorated the subsequent ICD exacerbation by S. aureus. These results suggest that even without barrier disruption, S. aureus colonization might affect epidermal cells and lead neutrophil infiltration, which may increase the susceptibility to inflammation. Targeting S. aureus colonization on healthy skin could be a new preventive therapeutic target of AD.

Skin colonized Staphylococcus aureus exacerbates the inflammation of murine irritant contact dermatitis via modulating innate immune pathways