Impact of Glycan Linkage to <i>Staphylococcus aureus</i> Wall Teichoic Acid on Langerin Recognition and Langerhans Cell Activation

Staphylococcus aureus is the leading cause of skin and soft tissue infections. It remains incompletely understood how skin-resident immune cells respond to invading S. contribute an effective response. Langerhans (LCs), only professional antigen-presenting cell type in epidermis, sense through their pattern-recognition receptor langerin, triggering a proinflammatory Langerin recognizes β-1,4-linked N-acetylglucosamine (β1,4-GlcNAc) but not α-1,4-linked GlcNAc (α1,4-GlcNAc) modifications, which are added by dedicated glycosyltransferases TarS TarM, respectively, on wall glycopolymer teichoic acid (WTA). Recently, alternative WTA glycosyltransferase, TarP, was identified, also modifies with β-GlcNAc at C-3 position (β1,3-GlcNAc) ribitol phosphate (RboP) subunit. Here, we aimed unravel impact linkage for langerin binding LC activation. Using genetically modified strains, observed that similarly recognized bacteria produce either TarS- or TarP-modified WTA, yet tarP-expressing induced increased cytokine production maturation vitro-generated LCs compared tarS-expressing aureus. Chemically synthesized molecules, representative different glycosylation patterns, were used identify langerin-WTA requirements. We established sufficient confer binding, thereby presenting synthetic molecules as novel glycobiology tool structure-binding studies elucidating molecular pathogenesis. Overall, our data suggest able all β-GlcNAc-WTA producing likely performing important role first responders upon invasion.