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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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Detalles Bibliográficos
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
Descripción
Sumario: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.