Epidermal host defense (antimicrobial) peptide gene expression in experimental dermatomycosis.

BURSTEIN VL; BECCACECE I; GUASCONI L; ALMEIDA M; MENA C; CERVI L; PISTORESI-PALENCIA MC; CHIAPELLO LS

Congreso; Reunión Conjunta SAIC - SAI - AAFE - NANOMED.AR. Sociedad Argentina de Inmunología. LXIX Reunión Anual de la Sociedad Argentina de Inmunología; 2021

EPIDERMAL HOST DEFENSE (ANTIMICROBIAL) PEPTIDE GENE EXPRESSION IN EXPERIMENTAL DERMATOMYCOSISHost defense antimicrobial peptides (HDP) are small proteins that directly kill or inhibit pathogen growth, modulate inflammation and skin homeostasis. Previously, we demonstrated that type 17 response is crucial to inhibit fungal proliferation after dermatophyte infection in C57BL/6 mice and, in the absence of a functional IL-17 pathway in IL-17RAKO mice, fungal burden was significantlyincreased compared to WT mice. However, the IL-17-mediated effector mechanisms that inhibit dermatophyte growth and the role of HDP remain undefined.The aim of this work was to evaluate the gene expression of theHDP β-defensins 2, 3 and 14 and calprotectin (S100A9) in the epidermisof C57BL/6 and IL-17RAKO mice at early time-points of Nannizziagypsea infection.C57BL/6 (WT) and IL-17RAKO mice were epicutaneously infectedwith a N. gypsea mycelia suspension (infected group) or treated withsterile saline solution (uninfected controls). On day 1 or 3 post-infection(dpi), skin was trypsinized, mRNA was extracted, cDNA wasgenerated and used for quantitative PCR with primers for mBD2,mBD3, mBD14, S100A9, GAPDH and β-actin genes.Dermatophyte-infected WT mice expressed lower levels of mBD2compared to uninfected controls by 1 dpi (p<0.01) and remained decreasedby 3 dpi (p<0.05) along with diminished mBD3 and mBD14expression (p<0.0001, p<0.001, 3-day infected mice vs controls). Onthe contrary, infected IL-17RAKO mice early expressed mBD2 andmBD14 mRNA by a 5- and 6-fold change respectively (p<0.0007,p<0.0012, compared to controls) and continued to be upregulatedby 3 dpi (p<0.0001, p<0.0007, respectively) along with an increasedexpression of mBD3 (p>0.003) and S100A9 (p>0.0001), comparedto controls.These data suggest that, in our model, the susceptibility to fungalskin infection in IL-17RAKO mice is uncoupled from mBD2, mBD3,mBD14 and S100A9 expression. Probably, the elevated fungalburden observed in IL-17RAKO induces HDP through IL-17 signalling-independent mechanisms.