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

BURSTEIN VL; BECCACECE, IGNACIO; GUASCONI, LORENA; ALMEIDA, MARIEL; MENA, CRISTIAN J.; CERVI L; PISTORESI, CRISTINA; CHIAPELLO, LAURA S.

Buenos Aires

Congreso; Reunión Conjunta SAIC. SAI. AAFE.NANOMED.AR.; 2021

Sociedad Argentina de Inmunología

Host 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 significantly increased 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 the HDP β-defensins 2, 3 and 14 and calprotectin (S100A9) in the epidermis of C57BL/6 and IL-17RAKO mice at early time-points of Nannizzia gypsea infection.C57BL/6 (WT) and IL-17RAKO mice were epicutaneously infected with a N. gypsea mycelia suspension (infected group) or treated with sterile saline solution (uninfected controls). On day 1 or 3 post-infection (dpi), skin was trypsinized, mRNA was extracted, cDNA was generated 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 mBD2 compared to uninfected controls by 1 dpi (p<0.01) and remained decreased by 3 dpi (p<0.05) along with diminished mBD3 and mBD14 expression (p<0.0001, p<0.001, 3-day infected mice vs controls). On the contrary, infected IL-17RAKO mice early expressed mBD2 and mBD14 mRNA by a 5- and 6-fold change respectively (p<0.0007, p<0.0012, compared to controls) and continued to be upregulated by 3 dpi (p<0.0001, p<0.0007, respectively) along with an increased expression of mBD3 (p>0.003) and S100A9 (p>0.0001), compared to controls.These data suggest that, in our model, the susceptibility to fungal skin infection in IL-17RAKO mice is uncoupled from mBD2, mBD3, mBD14 and S100A9 expression. Probably, the elevated fungal burden observed in IL-17RAKO induces HDP through IL-17 signalling-independent mechanisms.