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The impact of Staphylococcus aureus cell wall glycosylation on langerin recognition and Langerhans cell activation

View ORCID ProfileA Hendriks, R van Dalen, S Ali, D Gerlach, GA van der Marel, FF Fuchsberger, P Aerts, CJC de Haas, A Peschel, View ORCID ProfileC Rademacher, View ORCID ProfileJAG van Strijp, View ORCID ProfileJDC Codée, View ORCID ProfileNM van Sorge
doi: https://doi.org/10.1101/2020.11.06.371559
A Hendriks
1Medical Microbiology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
2GSK, Siena, Italy
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R van Dalen
1Medical Microbiology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
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S Ali
3Leiden Institute of Chemistry, Leiden University, Leiden, The Netherlands
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D Gerlach
4Interfaculty Institute of Microbiology and Infection Medicine, University of Tübingen, Tübingen, Germany
5German Centre for Infection Research (DZIF), Partner Site Tübingen, Tübingen, Germany
6Cluster of Excellence EXC2124 Controlling Microbes to Fight Infections
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GA van der Marel
3Leiden Institute of Chemistry, Leiden University, Leiden, The Netherlands
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FF Fuchsberger
7Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, Potsdam, Germany
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P Aerts
1Medical Microbiology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
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CJC de Haas
1Medical Microbiology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
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A Peschel
4Interfaculty Institute of Microbiology and Infection Medicine, University of Tübingen, Tübingen, Germany
5German Centre for Infection Research (DZIF), Partner Site Tübingen, Tübingen, Germany
6Cluster of Excellence EXC2124 Controlling Microbes to Fight Infections
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C Rademacher
7Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, Potsdam, Germany
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JAG van Strijp
1Medical Microbiology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
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JDC Codée
3Leiden Institute of Chemistry, Leiden University, Leiden, The Netherlands
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NM van Sorge
1Medical Microbiology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
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  • For correspondence: n.m.vansorge@amsterdamumc.nl
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Abstract

Staphylococcus aureus is the leading cause of skin and soft tissue infections. It remains incompletely understood how skin-resident immune cells respond to S. aureus invasion and contribute to an effective immune response. Langerhans cells (LCs), the only professional antigen-presenting cell type in the epidermis, sense S. aureus through their pattern-recognition receptor langerin, triggering a pro-inflammatory response. Langerin specifically recognizes the β-1,4-linked N-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-resistant S. aureus strains 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-modified S. aureus strains, we observed that langerin similarly recognized bacteria that produce either TarS- or TarP-modified WTA. Furthermore, using chemically-synthesized WTA, representative of the different S. aureus WTA glycosylation patterns, established that β-GlcNAc is sufficient to confer langerin binding. Functionally, tarP-expressing S. aureus induce increased cytokine production and maturation of in vitro-generated LCs compared to tarSexpressing S. aureus. Overall, our data suggest that LCs are able to sense all β-GlcNAc-WTA producing S. aureus strains, likely performing an important role as first responders upon S. aureus skin invasion.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • ↵& Current affiliation: Interfaculty Institute of Microbiology and Infection Medicine, University of Tübingen, Tübingen, Germany

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted November 07, 2020.
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The impact of Staphylococcus aureus cell wall glycosylation on langerin recognition and Langerhans cell activation
A Hendriks, R van Dalen, S Ali, D Gerlach, GA van der Marel, FF Fuchsberger, P Aerts, CJC de Haas, A Peschel, C Rademacher, JAG van Strijp, JDC Codée, NM van Sorge
bioRxiv 2020.11.06.371559; doi: https://doi.org/10.1101/2020.11.06.371559
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The impact of Staphylococcus aureus cell wall glycosylation on langerin recognition and Langerhans cell activation
A Hendriks, R van Dalen, S Ali, D Gerlach, GA van der Marel, FF Fuchsberger, P Aerts, CJC de Haas, A Peschel, C Rademacher, JAG van Strijp, JDC Codée, NM van Sorge
bioRxiv 2020.11.06.371559; doi: https://doi.org/10.1101/2020.11.06.371559

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