1. The impact ofStaphylococcus aureuscell wall glycosylation on langerin recognition and Langerhans cell activation
- Author
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Piet C. Aerts, van Strijp J, van der Marel G, Astrid Hendriks, Felix F. Fuchsberger, Andreas Peschel, van Sorge N, Shaukat Ali, Jeroen D. C. Codée, Christoph Rademacher, David Gerlach, de Haas C, and van Dalen R
- Subjects
0303 health sciences ,Teichoic acid ,Cell type ,Glycosylation ,Langerhans cell ,integumentary system ,Langerin ,biology ,medicine.disease_cause ,Microbiology ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Immune system ,medicine.anatomical_structure ,chemistry ,Staphylococcus aureus ,medicine ,biology.protein ,Receptor ,030304 developmental biology ,030215 immunology - Abstract
Staphylococcus aureusis the leading cause of skin and soft tissue infections. It remains incompletely understood how skin-resident immune cells respond toS. aureusinvasion and contribute to an effective immune response. Langerhans cells (LCs), the only professional antigen-presenting cell type in the epidermis, senseS. aureusthrough their pattern-recognition receptor langerin, triggering a pro-inflammatory response. Langerin specifically recognizes the β-1,4-linkedN-acetylglucosamine (β-GlcNAc) modification, which requires the glycosyltransferase TarS, on the cell wall glycopolymer Wall Teichoic Acid (WTA). Recently, an alternative WTA glycosyltransferase, TarP, was identified in methicillin-resistantS. aureusstrains belonging to clonal complexes (CC) 5 and CC398. TarP also modifies WTA with β-GlcNAc but at the C-3 position of the WTA ribitol phosphate (RboP) subunit. Here, we aimed to unravel the impact of β-GlcNAc linkage position for langerin binding and LC activation. In addition, we performed structure-binding studies using a small panel of unique chemically-synthesized WTA molecules to assess langerin-WTA binding requirements. Using FITC-labeled recombinant human langerin and genetically-modifiedS. aureusstrains, we observed that langerin similarly recognized bacteria that produce either TarS- or TarP-modified WTA. Furthermore, using chemically-synthesized WTA, representative of the differentS. aureusWTA glycosylation patterns, established that β-GlcNAc is sufficient to confer langerin binding. Functionally,tarP-expressingS. aureusinduce increased cytokine production and maturation ofin vitro-generated LCs compared totarSexpressingS. aureus. Overall, our data suggest that LCs are able to sense all β-GlcNAc-WTA producingS. aureusstrains, likely performing an important role as first responders uponS. aureusskin invasion.
- Published
- 2020