Human hair follicles (HF) engage in olfactory receptor (OR)-dependent chemosensation via OR2AT4 and continuous signaling is required for anagen maintenance ex vivo. OR2AT4 is expressed mainly in the suprabulbar outer root sheath (ORS) and selectively targeted by the synthetic sandalwood odorant (Sandalore®). Microarray analysis revealed that Sandalore® strongly up-regulates dermcidin (DCD) transcription in microdissected HFs ex vivo. DCD is an antimicrobial peptide with activity against S. aureus, S. epidermidis, P. aeruginosa and E. coli previously thought to be produced only by sweat gland epithelium. We asked whether Sandalore® I) up-regulates intrafollicular DCD peptide production, and II) renders organ-cultured human HFs less susceptible to bacterial contamination. By in situ hybridization and immunofluorescence microscopy epithelium of freshly embedded human scalp skin samples from 3 healthy donors, we show that, in vivo, DCD shows almost negligible mRNA and peptide expression in the HF epithelium and is mainly restricted to eccrine glands. After 6 days of HF stimulation with Sandalore® ex vivo, the intrafollicular production of DCD peptide in ORS keratinocytes was significantly increased, also after topical Sandalore® administration to organ-cultured human scalp skin. Importantly, Sandalore® significantly reduced microbial contamination of human scalp HFs organ-cultured in the absence of antibiotics. Moreover, the analysis of the culture medium of treated scalp skin suggest that Sandalore® affects microbial balancing. 
Thus, our data suggest that “olfactotherapy” of hair follicle diseases characterized by major microbial imbalances, such as acne vulgaris or bacterial folliculitis, with selected odorants could be beneficial.

Increasing follicular resistance to bacterial contamination: A novel antimicrobial therapy?