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

BECCACECE I; ALMEIDA M; BURSTEIN VL; GUASCONI L; MENA C; CHIAPELLO LS

Congreso; Reunión conjunta SAIC, SAI & FAIC SAFIS 2022; 2022

The skin is a physical barrier that protects the body against infectionsowing to several immune cell populations including two major subsetsof CD11c+ myeloid cells: Langerhans (LC) and dermal dendriticcells (DC). CARD9 expression (an adaptor molecule downstreampattern recognition receptors) in dendritic cells plays a central role inantifungal immunity, however, the tissue-specific innate immunity remainspoorly understood in dermatophytosis. In this study, we aim toinvestigate the in vivo role of skin CD11c+ cells in the susceptibility toexperimental dermatophytic infection. C57BL/6 (WT), CD11c-DTRGFP,Lang-eGFP-DTR or IL-17RA KO mice were epicutaneouslyinfected in the back with Nannizzia gypsea. To deplete CD11c+ cellsor LC, CD11c-DTR-GFP or Lang-eGFP-DTR mice (respectively),received a single dose of diphtheria-toxin (DT, 2 ng/g) 24 h prior toinfection. On 3- and 6-days post-infection (dpi), back skin was treatedwith Trypsin/EDTA (2 h/37°C) and epidermal cell suspension wasused to perform FACS analysis and to determine cytokines (ELISA),fungal burden and CARD9 gene expression by real time PCR. At anearly time-point of infection (3 dpi), only CD11c+cell-depleted miceshowed a significant increase in fungal burden compared to WT,Lang-eGFP-DTR or IL-17RAKO mice (P<0.05). In contrast, LC-depletedmice were not susceptible to infection and IL-17RAKO mice showed an elevated fungal burden from 6 dpi. The susceptibility ofCD11+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 analysisrevealed that CARD9 gene expression was exclusively detected inCD45+ cells in the skin. Taking together, these data suggest a criticalrole of CD11c+ cells, but not of the LC subset, in the innate controlof dermatophytosis. Further studies are underway to link the role ofdermal DC and CARD9 in early antifungal immunity to dermatophyteinfection in the skin.