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

Abstract

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.

Head and neck dermatitis is exacerbated by Malassezia furfur colonization, skin barrier disruption, and immune dysregulation

“…In addition, a recent study indicated that the sebum-microbial metabolite-IL-33 axis may play a role in initiating atopic dermatitis (42). M. furfur induces the expression of these cytokines in keratinocytes, which is further enhanced by the Th2 milieu in AD, which may contribute to the exacerbation of the disease (43).…”

Interactions between Malassezia and New Therapeutic Agents in Atopic Dermatitis Affecting Skin Barrier and Inflammation in Recombinant Human Epidermis Model

“…β-defensin2 and LL-37 stimulate T-cells to secrete inflammatory cytokines such as IL-4, IL-13, and IL-31 to regulate the itch sensation and increase vascular permeability [ 45 ]. We previously showed that Malassezia increases β-defensin2 production in human keratinocytes [ 14 ]. In our study, the MR-treated groups had significantly higher levels of β-defensin2 and LL-37 compared to the MR-untreated groups ( Figure 2 and Figure S2 ).…”

“…Malassezia is recognized as a pathogen in various skin disorders, including seborrheic dermatitis, pityriasis versicolor, Malassezia folliculitis, and head and neck dermatitis in AD, and psoriasis, in immunologically competent hosts [ 12 , 13 ]. The cell wall components of Malassezia species bind to multiple receptors on the host cell membrane, resulting in ligand internalization and activation of the NLRP3 inflammasome as well as inflammatory signaling pathways, including the mitogen-activated protein kinase (MAPK), nuclear factor kappa B (NF-κB), and nuclear factor of activated T cells (NFAT) pathways [ 14 , 15 ]. For example, pathogen-associated molecular patterns (PAMPs) on the cell surface of Malassezia are recognized by toll-like receptors (TLRs) on host keratinocytes and activate inflammation.…”

“…Malassezia species do not typically cause sensitization in healthy people, but a significant portion of AD patients show increased serum immunoglobulin E to Malassezia [ 15 ]. Among the 14 identified species of Malassezia , M. sympodialis , M. globosa, M. furfur, and M. restricta have been studied with respect to various human skin diseases [ 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 ]. M. restricta, M. globosa, and M. sympodialis are the most frequently identified species in AD skin [ 19 ].…”

Malassezia Folliculitis in the Setting of COVID-19

“…Interestingly, M. globosa responds favorably in vitro over other species to high temperatures and the components of sweat [ 18 ], which suggests a link between this observed predominance and risk factors associated with MF. A recent study observed M. globosa ’s heightened ability to induce inflammasome-mediated inflammation [ 19 ].…”