Staphylococcus aureus skin colonization is enhanced by the interaction of neutrophil extracellular traps with keratinocytes

Abstract Staphylococcus aureus is a facultative pathogen found on skin and nasal surfaces. It is usually absent from the skin of healthy humans but frequently colonizes the skin of atopic dermatitis patients. Here we investigate the functional role of neutrophils in the initial steps of S. aureus skin colonization and how skin commensals modulate the S. aureus-induced recruitment of neutrophils to the skin. By using an epicutaneous mouse skin colonization model we show that skin inflammation induced by tape-stripping leads to a rapid recruitment of neutrophils which correlates with enhanced S. aureus skin colonization. Interestingly, depletion of neutrophils in vivo reduces S. aureus colonization and in vitro co-culture of primary human keratinocytes with neutrophils promotes S. aureus adherence. We demonstrate that the interaction of neutrophil extracellular traps (NETs) with keratinocytes are responsible for increased S. aureus skin colonization. Finally, we show that S. epidermidis as part of the skin microbiota can reduce neutrophil recruitment induced by S. aureus infection. These data suggest that microbiota-mediated skin protection against S. aureus is dampened in an inflammatory environment in which NETs released by infiltrating neutrophils unexpectedly contribute to enhanced S. aureus skin colonization.