Staphylococcus aureus is a major cause of skin and soft tissue infections and aggravator of the inflammatory skin disease atopic dermatitis (AD [eczema]). Epicutaneous exposure to S. aureus induces Th17 responses through skin Langerhans cells (LCs), which paradoxically contribute to host defense but also to AD pathogenesis. The molecular mechanisms underlying the interaction between S. aureus and LCs are poorly understood. Here we demonstrate that human LCs directly interact with S. aureus through the pattern recognition receptor langerin (CD207). Human, but not mouse, langerin interacts with S. aureus through the conserved β-N-acetylglucosamine (GlcNAc) modifications on wall teichoic acid (WTA), thereby discriminating S. aureus from other staphylococcal species. Importantly, the specific S. aureus WTA glycoprofile strongly influences the level of proinflammatory cytokines that are produced by in vitro-generated LCs. Finally, in a murine epicutaneous infection model, S. aureus strongly upregulated transcripts of Cxcl1, Il6, and Il17, which required the presence of both human langerin and WTA β-GlcNAc. Our findings provide molecular insight into the unique proinflammatory capacities of S. aureus in relation to skin inflammation. IMPORTANCE The bacterium Staphylococcus aureus is an important cause of skin infections and is also associated with the occurrence and severity of eczema. Langerhans cells (LCs), a specific subset of skin immune cells, participate in the immune response to S. aureus, but it is yet unclear how LCs recognize S. aureus. Therefore, we investigated the molecular mechanism underlying the interaction between LCs and S. aureus. We identified that wall teichoic acid, an abundant polymer on the S. aureus surface, is recognized by langerin, a receptor unique to LCs. This interaction allows LCs to discriminate S. aureus from other related staphylococcal species and initiates a proinflammatory response similar to that observed in patients with eczema. Our data therefore provide important new insights into the relationship between S. aureus, LCs, and eczema.

No abstract

No abstract

SummaryStaphylococcus aureus is a major cause of skin and soft tissue infections and aggravator of the inflammatory skin disease atopic dermatitis (AD). Langerhans cells (LCs) initiate a Th17 response upon exposure to S. aureus, which contributes to host defense but also to AD pathogenesis. However, the molecular mechanisms underlying the unique pro-inflammatory capacities of S. aureus remain unclear. We demonstrate that human LCs directly interact with S. aureus through the pattern-recognition receptor langerin (CD207), which specifically recognizes the conserved β-N-acetylglucosamine (GlcNAc) modifications of wall teichoic acid (WTA) that are not expressed by other staphylococcal species. The WTA glycoprofile strongly influences the production of Th1-and Th17-polarizing cytokines by LCs. Specifically, β-GlcNAc activates LCs, whereas co-decoration of WTA with α-GlcNAc through the enzyme TarM, uniformly present in the AD-associated CC1 lineage, attenuates LC immune activation. Our findings provide important mechanistic insights into the role of S. aureus in inflammatory skin disease.

V, et al. Genomic analysis identifies new drivers and progression pathways in skin basal cell carcinoma. Nat Genet 2016;48:398e406.