Langerhans Cells Sense Staphylococcus aureus Wall Teichoic Acid through Langerin To Induce Inflammatory Responses

• Published in: mBio 2019-05, Vol.10 (3)
• Main Authors: van Dalen, Rob, De La Cruz Diaz, Jacinto S, Rumpret, Matevž, Fuchsberger, Felix F, van Teijlingen, Nienke H, Hanske, Jonas, Rademacher, Christoph, Geijtenbeek, Teunis B H, van Strijp, Jos A G, Weidenmaier, Christopher, Peschel, Andreas, Kaplan, Daniel H, van Sorge, Nina M
• Format: Article
• Language: English
• Subjects: Acetylglucosamine; Animals; Antigens, CD - genetics; Antigens, CD - immunology; Antigens, Surface - genetics; Antigens, Surface - immunology; Cells, Cultured; Cytokines - genetics; Cytokines - immunology; Host-Microbe Biology; Humans; Inflammation; Interleukin-17 - genetics; Interleukin-17 - immunology; Langerhans Cells - immunology; Lectins, C-Type - genetics; Lectins, C-Type - immunology; Mannose-Binding Lectins - genetics; Mannose-Binding Lectins - immunology; Mice; Mice, Inbred C57BL; Skin - immunology; Skin - microbiology; Staphylococcal Infections - immunology; Staphylococcus aureus; Teichoic Acids - immunology
• ISSN: 2161-2129; 2150-7511
• DOI: 10.1128/mBio.00330-19

is a major cause of skin and soft tissue infections and aggravator of the inflammatory skin disease atopic dermatitis (AD [eczema]). Epicutaneous exposure to 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 and LCs are poorly understood. Here we demonstrate that human LCs directly interact with through the pattern recognition receptor langerin (CD207). Human, but not mouse, langerin interacts with through the conserved β- acetylglucosamine (GlcNAc) modifications on wall teichoic acid (WTA), thereby discriminating from other staphylococcal species. Importantly, the specific WTA glycoprofile strongly influences the level of proinflammatory cytokines that are produced by -generated LCs. Finally, in a murine epicutaneous infection model, strongly upregulated transcripts of , , and , which required the presence of both human langerin and WTA β-GlcNAc. Our findings provide molecular insight into the unique proinflammatory capacities of in relation to skin inflammation. The bacterium 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 , but it is yet unclear how LCs recognize Therefore, we investigated the molecular mechanism underlying the interaction between LCs and We identified that wall teichoic acid, an abundant polymer on the surface, is recognized by langerin, a receptor unique to LCs. This interaction allows LCs to discriminate 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 , LCs, and eczema.