Inflammasome-mediated Inflammation by Malassezia in human keratinocytes: A comparative analysis with different strains

Malassezia species are associated with several common dermatologic conditions including pityriasis versicolor, seborrhoeic dermatitis, folliculitis, and atopic dermatitis and dandruff. However, its causal role remains to be established. We intended to explore the role of inflammasome activation in human keratinocytes in response to three different Malassezia species. We compared the different activation patterns of inflammasomes and the expression of pro-inflammatory cytokines and antimicrobial peptides by three different Malassezia species—M. restricta, M. globosa and M. sympodialis—in human keratinocytes. We found that different Malassezia species, especially M. restricta and M. globosa could induce nucleotide-binding oligomerisation domain, leucine-rich repeat and pyrin-domain-containing protein (NLRP)3–apoptosis-associated speck-like protein containing CARD (ASC) inflammasome activation and subsequent interleukin (IL)-1β secretion in human keratinocytes. Malassezia species variably induced thymic stromal lymphopoietin, β-defensin 2, and LL-37. IL-8 mRNA and IL-22 protein significantly increased in the M. sympodialis-treated group, and Chemokine C–C motif ligand (CCL)17 and CCL22 mRNA were increased in response to M. globosa- and M. restricta- treated keratinocytes, respectively. Our data show that various species of Malassezia promote variable inflammatory responses in keratinocytes by activating NLRP3 inflammasomes, pro-inflammatory cytokines and chemokines, and antimicrobial peptides.