Malassezia globosa induce differentiation of pathogenic Th17 cells by inducing IL-23 secretion by keratinocytes

Abstract Malassezia, the most abundant fungal commensal on the mammalian skin, has been linked to several inflammatory skin diseases such as atopic dermatitis, seborrheic dermatitis and psoriasis. This study reveals that epicutaneous application with Malassezia globosa triggers skin inflammation in mice. RNA-sequencing of the resulting mouse lesions indicates activation of IL-17 signaling and Th17 cells differentiation pathways by Malassezia globosa. Furthermore, our findings demonstrate a significant upregulation of IL-23, IL-23R, IL-17A, and IL-22 expressions, along with an increase in the proportion of Th17 and pathogenic Th17 cells in mouse skin exposed to Malassezia globosa. In vitro experiments illustrate that Malassezia globosa prompts human primary keratinocytes to secrete IL-23 via TLR2-MyD88-NF-κB signaling. This IL-23 secretion by keratinocytes is shown to be adequate for inducing the differentiation of pathogenic Th17 cells in the skin. Overall, these results underscore the significant role of Malassezia in exacerbating skin inflammation by stimulating IL-23 secretion by keratinocytes and promoting the differentiation of pathogenic Th17 cells.