The effects of staphylococci on keratinocytes, with a view to understanding the pathogenesis of atopic dermatitis

Background: Atopic dermatitis (AD) is a common chronic inflammatory skin disease, which significantly impairs patients’ quality of life. A typical AD feature is colonisation and infection of the skin with Staphylococcus aureus, which leads to loss of commensal staphylococci (Staphylococcus epidermidis) from the skin. Although S. epidermidis and S. aureus have many similarities, S. aureus is a major cause of skin infections, unlike S. epidermidis, which is abundant in normal skin. The balance between S. epidermidis and S. aureus is disturbed in AD and there is increasing evidence that microbial dysbiosis is associated with AD pathogenesis. Hypothesis: Skin cells respond differently to commensal staphylococci (S. epidermidis) and bacteria associated with skin infections, such as S. aureus. Results: Cell-suspensions and filter-sterilised supernatants of most S. aureus strains induced human-beta-defensin (HBD)-3 production in cultured keratinocytes and skin equivalents, measured by enzyme-linked immunosorbent assay (ELISA), whereas S. epidermidis and a minority of S. aureus strains did not. The S. aureus factor(s) responsible for the HBD-3 induction were found to be heat-stable and likely proteinaceous. Candidate S. aureus proteins were identified using ion-exchange chromatography and mass spectrometry and their HBD-3-inducing capacity was tested. Phenotypic characterisation indicated compounds that may favour S. epidermidis over S. aureus growth. Discussion: S. epidermidis and S. aureus have a different effect on HBD-3 induction in keratinocytes. This suggests that the skin has evolved an effective defence strategy against S. aureus (HBD-3 production) and a means of triggering this response specifically to non-commensal staphylococci by detecting a cell component unique to S. aureus. AD patients have increased susceptibility to S. aureus infection. If disruption of the skin microbial balance is proven to be able to trigger AD, or if restoration of skin flora can resolve AD, this would suggest that skin microbial dysbiosis is a key factor in AD pathogenesis.