Langerhans Cells Sense <italic toggle="yes">Staphylococcus aureus</italic> Wall Teichoic Acid through Langerin To Induce Inflammatory Responses

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 de...

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Autores principales:	Rob van Dalen, Jacinto S. De La Cruz Diaz, Matevž Rumpret, Felix F. Fuchsberger, Nienke H. van Teijlingen, Jonas Hanske, Christoph Rademacher, Teunis B. H. Geijtenbeek, Jos A. G. van Strijp, Christopher Weidenmaier, Andreas Peschel, Daniel H. Kaplan, Nina M. van Sorge
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	atopic dermatitis glycosylation Langerhans cell langerin Staphylococcus aureus wall teichoic acid Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/5381197dcad241c8928ae7c4eb2becaf
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spelling	oai:doaj.org-article:5381197dcad241c8928ae7c4eb2becaf2021-11-15T15:55:24ZLangerhans Cells Sense <italic toggle="yes">Staphylococcus aureus</italic> Wall Teichoic Acid through Langerin To Induce Inflammatory Responses10.1128/mBio.00330-192150-7511https://doaj.org/article/5381197dcad241c8928ae7c4eb2becaf2019-06-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00330-19https://doaj.org/toc/2150-7511ABSTRACT 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.Rob van DalenJacinto S. De La Cruz DiazMatevž RumpretFelix F. FuchsbergerNienke H. van TeijlingenJonas HanskeChristoph RademacherTeunis B. H. GeijtenbeekJos A. G. van StrijpChristopher WeidenmaierAndreas PeschelDaniel H. KaplanNina M. van SorgeAmerican Society for Microbiologyarticleatopic dermatitisglycosylationLangerhans celllangerinStaphylococcus aureuswall teichoic acidMicrobiologyQR1-502ENmBio, Vol 10, Iss 3 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	atopic dermatitis glycosylation Langerhans cell langerin Staphylococcus aureus wall teichoic acid Microbiology QR1-502
spellingShingle	atopic dermatitis glycosylation Langerhans cell langerin Staphylococcus aureus wall teichoic acid Microbiology QR1-502 Rob van Dalen Jacinto S. De La Cruz Diaz Matevž Rumpret Felix F. Fuchsberger Nienke H. van Teijlingen Jonas Hanske Christoph Rademacher Teunis B. H. Geijtenbeek Jos A. G. van Strijp Christopher Weidenmaier Andreas Peschel Daniel H. Kaplan Nina M. van Sorge Langerhans Cells Sense <italic toggle="yes">Staphylococcus aureus</italic> Wall Teichoic Acid through Langerin To Induce Inflammatory Responses
description	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.
format	article
author	Rob van Dalen Jacinto S. De La Cruz Diaz Matevž Rumpret Felix F. Fuchsberger Nienke H. van Teijlingen Jonas Hanske Christoph Rademacher Teunis B. H. Geijtenbeek Jos A. G. van Strijp Christopher Weidenmaier Andreas Peschel Daniel H. Kaplan Nina M. van Sorge
author_facet	Rob van Dalen Jacinto S. De La Cruz Diaz Matevž Rumpret Felix F. Fuchsberger Nienke H. van Teijlingen Jonas Hanske Christoph Rademacher Teunis B. H. Geijtenbeek Jos A. G. van Strijp Christopher Weidenmaier Andreas Peschel Daniel H. Kaplan Nina M. van Sorge
author_sort	Rob van Dalen
title	Langerhans Cells Sense <italic toggle="yes">Staphylococcus aureus</italic> Wall Teichoic Acid through Langerin To Induce Inflammatory Responses
title_short	Langerhans Cells Sense <italic toggle="yes">Staphylococcus aureus</italic> Wall Teichoic Acid through Langerin To Induce Inflammatory Responses
title_full	Langerhans Cells Sense <italic toggle="yes">Staphylococcus aureus</italic> Wall Teichoic Acid through Langerin To Induce Inflammatory Responses
title_fullStr	Langerhans Cells Sense <italic toggle="yes">Staphylococcus aureus</italic> Wall Teichoic Acid through Langerin To Induce Inflammatory Responses
title_full_unstemmed	Langerhans Cells Sense <italic toggle="yes">Staphylococcus aureus</italic> Wall Teichoic Acid through Langerin To Induce Inflammatory Responses
title_sort	langerhans cells sense <italic toggle="yes">staphylococcus aureus</italic> wall teichoic acid through langerin to induce inflammatory responses
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/5381197dcad241c8928ae7c4eb2becaf
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Langerhans Cells Sense <italic toggle="yes">Staphylococcus aureus</italic> Wall Teichoic Acid through Langerin To Induce Inflammatory Responses

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