Staphylococcus aureuswall teichoic acid is a pathogen-associated molecular pattern that is recognized by langerin (CD207) on skin Langerhans cells

AbstractStaphylococcus aureusis a major cause of skin and soft tissue infections and aggravator of the inflammatory skin disease atopic dermatitis (AD). Epicutaneous exposure toS. aureusinduces Th17 responses through skin Langerhans cells (LCs), which paradoxically contribute to host defense but also to AD pathogenesis. The underlying molecular mechanisms of the association betweenS. aureusand skin inflammation are poorly understood. Here, we demonstrate that human LCs directly interact withS. aureusthrough the pattern-recognition receptor langerin (CD207). Human, but not mouse, langerin interacts withS. aureusthrough the conserved β-N-acetylglucosamine (GlcNAc) modifications on wall teichoic acid (WTA), thereby discriminatingS. aureusfrom other staphylococcal species. Importantly, the specificS. aureusWTA glycoprofile strongly influences the level of Th1-and Th17-polarizing cytokines that are produced byin vitrogenerated LCs. Finally, in a murine epicutaneous infection model,S. aureusinduced a more pronounced influx of inflammatory cells and pro-inflammatory cytokine transcripts in skin of human langerin transgenic mice compared to wild-type mice. Our findings provide molecular insight into the unique pro-inflammatory capacities ofS. aureusin relation to inflammatory skin disease.