Conditional depletion of CD11c-expressing cells greatly compromises innate resistance to skin fungal infection

Congreso; Reunión Anual de Sociedades de Biociencias. LXVII Reunión Anual de la Sociedad Argentina de Investigación Clínica. LXX Reunión Anual de la Sociedad de Argentina de Inmunología. 3rd French-Argentine Immunology Congress. Reunión Anual 2022 de la Sociedad Ar; 2022

The skin is a physical barrier that protects the body against infections owing to several immune cell populations including two major subsets of CD11c+ myeloid cells: Langerhans (LC) and dermal dendritic cells (DC). CARD9 expression (an adaptor molecule downstream pattern recognition receptors) in dendritic cells plays a central role in antifungal immunity, however, the tissue-specific innate immunity remains poorly understood in dermatophytosis. In this study, we aim to investigate the in vivo role of skin CD11c+ cells in the susceptibility to experimental dermatophytic infection.C57BL/6 (WT), CD11c-DTR-GFP, Lang-eGFP-DTR or IL-17RA KO mice were epicutaneously infected in the back with Nannizzia gypsea. To deplete CD11c+ cells or LC, CD11c-DTR-GFP or Lang-eGFP-DTR mice (respectively), received a single dose of diphtheria-toxin (DT, 2 ng/g) 24 h prior to infection. On 3- and 6-days post-infection (dpi), back skin was treated with Trypsin/EDTA (2 h/37°C) and epidermal cell suspension was used to perform FACS analysis and to determine cytokines (ELISA), fungal burden and CARD9 gene expression by real time PCR.At an early time-point of infection (3 dpi), only CD11c+cell-depleted mice showed a significant increase in fungal burden compared to WT, Lang-eGFP-DTR or IL-17RAKO mice (P<0.05). In contrast, LC-depleted mice were not susceptible to infection and IL-17RAKO mice showed an elevated fungal burden from 6 dpi. The susceptibility of CD11+cell-depleted mice correlated with a reduction in IL-23, TNF, IL-12, IFN-γ, IL-1β and IL-17A. On the other hand, PCR analysis revealed that CARD9 gene expression was exclusively detected in CD45+ cells in the skin.Taking together, these data suggest a critical role of CD11c+ cells, but not of the LC subset, in the innate control of dermatophytosis. Further studies are underway to link the role of dermal DC and CARD9 in early antifungal immunity to dermatophyte infection in the skin.