Staphylococcus aureus induces the expression of tumor necrosis factor-alpha in primary human keratinocytes

Staphylococcus aureus induces inflammatory cytokines and causes skin inflammatory diseases, but infection parameters leading to cytokine induction are poorly understood in keratinocytes, the primary skin cells to interface with S. aureus.

Human primary keratinocytes were infected with S. aureus under various conditions to identify properties of infection that cause the induction of tumor necrosis factor-alpha (TNF-alpha), a proinflammatory cytokine that initiates host inflammatory responses.

Staphylococcus aureus induced TNF-alpha mRNA and protein in a dose-dependent manner. Cytochalasin D, an inhibitor of actin polymerization and S. aureus invasion, failed to prevent the induction of TNF-alpha, indicating that invasion was not a requirement. Furthermore, ultraviolet-, heat-, and gentamicin-treated bacteria did not induce TNF-alpha, suggesting that de novo bacterial protein synthesis of viable bacteria was required. Finally, S. aureus infection of primary human keratinocytes also led to an induction of the TNF-alpha receptor, TNFR1 (p55).

Early (preinvasion) S. aureus-keratinocyte surface interactions that require protein synthesis induce TNF-alpha. Bacterial surface components embedded within the cell wall do not suffice as TNF-alpha mediators, but require active protein synthesis and/or the accompaniment of secreted bacterial products. Furthermore, S. aureus infection leads to the specific induction of the TNF-alpha receptor TNFR1, but not TNFR2.