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

PLoS Pathogens
Florian SparberSalomé LeibundGut-Landmann

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 respon...Continue Reading

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Citations

Nov 16, 2019·The Journal of Experimental Medicine·Junjie ZhaoXiaoxia Li
Jan 5, 2020·Science Immunology·Sarah L Gaffen, Niki M Moutsopoulos
Feb 25, 2020·Journal of Dental Research·A H HovavI Prinz
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Apr 25, 2019·Pathogens·Florian Sparber, Salomé LeibundGut-Landmann
Jan 23, 2021·Journal of Dental Research·S WaldA H Hovav
Jan 16, 2021·Science·Timothy J BreakMichail S Lionakis
Dec 30, 2021·Virulence·José Pedro Lopes, Michail S Lionakis

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Methods Mentioned

BETA
flow cytometry
FACS
dissection
FCS
PCR

Software Mentioned

GraphPad Prism
FlowJo

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