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MBio. 2019 May 14;10(3). pii: e00330-19. doi: 10.1128/mBio.00330-19.

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

Author information

1
Medical Microbiology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
2
Departments of Dermatology and Immunology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
3
Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, Potsdam, Germany.
4
Department of Experimental Immunology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
5
Interfaculty Institute of Microbiology and Infection Medicine, University of Tübingen, Tübingen, Germany.
6
German Center for Infection Research (DZIF), Tübingen, Germany.
7
Medical Microbiology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands nsorge3@umcutrecht.nl.
#
Contributed equally

Abstract

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.

KEYWORDS:

Langerhans cell; Staphylococcus aureus ; atopic dermatitis; glycosylation; langerin; wall teichoic acid

PMID:
31088921
PMCID:
PMC6520447
DOI:
10.1128/mBio.00330-19
[Indexed for MEDLINE]
Free PMC Article

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