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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 (2018). Langerin+ DCs regulate innate IL-17 production in the oral mucosa during Candida albicans-mediated infection. PLoS Pathogens, 14(5):e1007069.

Abstract

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.

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:05 Vetsuisse Faculty > Veterinärwissenschaftliches Institut > Institute of Virology
04 Faculty of Medicine > Institute of Experimental Immunology
Dewey Decimal Classification:570 Life sciences; biology
Scopus Subject Areas:Life Sciences > Parasitology
Life Sciences > Microbiology
Life Sciences > Immunology
Life Sciences > Molecular Biology
Life Sciences > Genetics
Life Sciences > Virology
Language:English
Date:2018
Deposited On:20 Jul 2018 15:17
Last Modified:19 Oct 2024 01:35
Publisher:Public Library of Science (PLoS)
ISSN:1553-7366
OA Status:Gold
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.1371/journal.ppat.1007069
PubMed ID:29782555
Project Information:
  • Funder: SNSF
  • Grant ID: PP00P3_150758
  • Project Title: Host defense against fungal infections
  • Funder: H2020
  • Grant ID: 677200
  • Project Title: Immune Regulation - How Infection History Shapes the Immune System: Pathogen-induced Changes in Regulatory T Cells
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  • Content: Published Version
  • Language: English
  • Licence: Creative Commons: Attribution 4.0 International (CC BY 4.0)

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