Objectives: 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 aimed at identifying the cell types that produce IL-17 at the onset of infection, before adaptive immunity is activated, and to decipher how this innate response is regulated.
Methods: We used intracellular cytokine staining and flow cytometry to dissect at a single cell level the cytokine-producing lymphoid and myeloid subsets in the infected tissue of mice that were sublingually infected with C. albicans strain SC5314.
Results: For the first time, 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. The presence/existence of these 3 functionally redundant lymphocytes renders the protective IL-17 response against C. albicans highly robust.  IL-23, IL-1 and IL-6 contribute in a partially non-redundant manner to the production of IL-17. A careful characterization of the myeloid cell compartment in the murine tongue revealed that the three IL-17-instructive cytokines were provided by multiple overlapping cellular subsets in the infected tongue comprising tissue-resident Zbtb46+Langerin+ and Zbtb46-Langerin- mononuclear phagocytes as well as infiltrating Ly6G+CD11b+ neutrophils. 
Conclusion: Our work identified three distinct sources of innate IL-17 induction and revealed that complementary myeloid subsets cooperate for orchestrating the induction of innate IL-17-dependent antifungal immunity in the oral mucosa via IL-23, IL-1β and IL-6.

Regulation of innate IL-17 response to Candia albicans in the oral mucosa