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Langerin(+) DCs regulate innate IL-17 production in the oral mucosa during Candida albicans-mediated infection

The opportunistic fungal pathogen Candida albicans frequently causes diseases such as oropharyngeal candidiasis (OPC) in immunocompromised individuals. Although it is well appreciated that the cytokine IL-17 is crucial for protective immunity against OPC, the cellular source and the regulation of th...

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Autores principales: Sparber, Florian, Dolowschiak, Tamas, Mertens, Sarah, Lauener, Laura, Clausen, Björn E., Joller, Nicole, Stoitzner, Patrizia, Tussiwand, Roxane, LeibundGut-Landmann, Salomé
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5983869/
https://www.ncbi.nlm.nih.gov/pubmed/29782555
http://dx.doi.org/10.1371/journal.ppat.1007069
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author Sparber, Florian
Dolowschiak, Tamas
Mertens, Sarah
Lauener, Laura
Clausen, Björn E.
Joller, Nicole
Stoitzner, Patrizia
Tussiwand, Roxane
LeibundGut-Landmann, Salomé
author_facet Sparber, Florian
Dolowschiak, Tamas
Mertens, Sarah
Lauener, Laura
Clausen, Björn E.
Joller, Nicole
Stoitzner, Patrizia
Tussiwand, Roxane
LeibundGut-Landmann, Salomé
author_sort Sparber, Florian
collection PubMed
description The opportunistic fungal pathogen Candida albicans frequently causes diseases such as oropharyngeal candidiasis (OPC) in immunocompromised individuals. Although it is well appreciated that the cytokine IL-17 is crucial for protective immunity against OPC, the cellular source and the regulation of this cytokine during infection are still a matter of debate. Here, we directly visualized IL-17 production in the tongue of experimentally infected mice, thereby demonstrating that this key cytokine is expressed by three complementary subsets of CD90(+) leukocytes: RAG-dependent αβ and γδ T cells, as well as RAG-independent ILCs. To determine the regulation of IL-17 production at the onset of OPC, we investigated in detail the myeloid compartment of the tongue and found a heterogeneous and dynamic mononuclear phagocyte (MNP) network in the infected tongue that consists of Zbtb46(-)Langerin(-) macrophages, Zbtb46(+)Langerin(+) dendritic cells (DCs) and Ly6C(+) inflammatory monocytes. Of those, the Langerin(+) DC population stands out by its unique capacity to co-produce the cytokines IL-1β, IL-6 and IL-23, all of which promote IL-17 induction in response to C. albicans in the oral mucosa. The critical role of Langerin(+) DCs for the innate IL-17 response was confirmed by depletion of this cellular subset in vivo, which compromised IL-17 induction during OPC. In conclusion, our work revealed key regulatory factors and their cellular sources of innate IL-17-dependent antifungal immunity in the oral mucosa.
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spelling pubmed-59838692018-06-17 Langerin(+) DCs regulate innate IL-17 production in the oral mucosa during Candida albicans-mediated infection Sparber, Florian Dolowschiak, Tamas Mertens, Sarah Lauener, Laura Clausen, Björn E. Joller, Nicole Stoitzner, Patrizia Tussiwand, Roxane LeibundGut-Landmann, Salomé PLoS Pathog Research Article The opportunistic fungal pathogen Candida albicans frequently causes diseases such as oropharyngeal candidiasis (OPC) in immunocompromised individuals. Although it is well appreciated that the cytokine IL-17 is crucial for protective immunity against OPC, the cellular source and the regulation of this cytokine during infection are still a matter of debate. Here, we directly visualized IL-17 production in the tongue of experimentally infected mice, thereby demonstrating that this key cytokine is expressed by three complementary subsets of CD90(+) leukocytes: RAG-dependent αβ and γδ T cells, as well as RAG-independent ILCs. To determine the regulation of IL-17 production at the onset of OPC, we investigated in detail the myeloid compartment of the tongue and found a heterogeneous and dynamic mononuclear phagocyte (MNP) network in the infected tongue that consists of Zbtb46(-)Langerin(-) macrophages, Zbtb46(+)Langerin(+) dendritic cells (DCs) and Ly6C(+) inflammatory monocytes. Of those, the Langerin(+) DC population stands out by its unique capacity to co-produce the cytokines IL-1β, IL-6 and IL-23, all of which promote IL-17 induction in response to C. albicans in the oral mucosa. The critical role of Langerin(+) DCs for the innate IL-17 response was confirmed by depletion of this cellular subset in vivo, which compromised IL-17 induction during OPC. In conclusion, our work revealed key regulatory factors and their cellular sources of innate IL-17-dependent antifungal immunity in the oral mucosa. Public Library of Science 2018-05-21 /pmc/articles/PMC5983869/ /pubmed/29782555 http://dx.doi.org/10.1371/journal.ppat.1007069 Text en © 2018 Sparber et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Sparber, Florian
Dolowschiak, Tamas
Mertens, Sarah
Lauener, Laura
Clausen, Björn E.
Joller, Nicole
Stoitzner, Patrizia
Tussiwand, Roxane
LeibundGut-Landmann, Salomé
Langerin(+) DCs regulate innate IL-17 production in the oral mucosa during Candida albicans-mediated infection
title Langerin(+) DCs regulate innate IL-17 production in the oral mucosa during Candida albicans-mediated infection
title_full Langerin(+) DCs regulate innate IL-17 production in the oral mucosa during Candida albicans-mediated infection
title_fullStr Langerin(+) DCs regulate innate IL-17 production in the oral mucosa during Candida albicans-mediated infection
title_full_unstemmed Langerin(+) DCs regulate innate IL-17 production in the oral mucosa during Candida albicans-mediated infection
title_short Langerin(+) DCs regulate innate IL-17 production in the oral mucosa during Candida albicans-mediated infection
title_sort langerin(+) dcs regulate innate il-17 production in the oral mucosa during candida albicans-mediated infection
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5983869/
https://www.ncbi.nlm.nih.gov/pubmed/29782555
http://dx.doi.org/10.1371/journal.ppat.1007069
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