O9 Malassezia globosa induces a psoriatic phenotype in organotypic skin models
Styliani Mavrova, Kalum Clayton, Fei-Ling Lim, Jenny Pople, Mark Fowler, Andres Vallejo Pulido, Michael Ardern-JonesAbstract
Introduction and aims
Malassezia species have been found at higher loads in common skin conditions compared with healthy skin. Whether they drives host responses towards specific cutaneous inflammatory phenotypes or act as an opportunistic microbe at inflammation sites remains unclear. We set out to characterize the keratinocyte transcriptional response to Malassezia globosa (MG) and Malassezia furfur (MF) using a reconstituted human epidermis (RHE) model composed of differentiated keratinocytes, and to identify species-specific host–pathogen interactions.
Methods
RHE models were stimulated with MG and MF under varied dose and timepoint conditions and sequenced (Illumina NovaSeq6000). Transcriptomic data were analysed using R and checked for quality control (MultiQC), before data analysis (Kallisto, tximport and edgeR) and comparison with healthy or psoriasis lesions (GSE173706). Ontology was assessed using functional enrichment analyses (iDEP, ShinyGO and VissE Cloud) and ingenuity pathway analysis. RHE inflammatory protein expression was also evaluated (Olink Target 48 Cytokine Panel).
Results
MF-stimulation induced 4052 DEGs compared with 14 458 DEGs following MG-stimulation (P < 0.05, false discovery rate = 0.05). Principal component analysis revealed species-dependent clustering in the keratinocyte response to Malassezia. Both Malassezia species induced barrier-related transcripts and proinflammatory cytokines (CXCL1, CXCL8, CCL20) and upregulated interleukin (IL)36G. MG induced additional cytokines (IL17C, IL23A, TNFAIP6 and IRAK2), demonstrating a 42% overlap with a psoriasis disease network, indicating shared upstream regulators and the upregulation of IL17 and tumour necrosis factor pathway-related molecules. Contrastingly, MF induced lipid metabolism-associated transcripts (CYP4F22). Protein analysis confirmed MG upregulation of key immune mediators (IL1β, IL18, IL6, IL17C, TNF, CCL2, CXCL8 and GM-CSF). MG-induced keratinocyte signatures were recapitulated in psoriatic keratinocyte single-cell RNA-sequencing data, identifying the IL36G–IFNAR2 signalling axis as a link between epidermal and inflammatory responses.
Conclusions
Malassezia species elicit divergent keratinocyte transcriptomic signatures. MG promotes a psoriasis-like inflammatory profile, while MF favours a barrier-focused response with metabolic adaptation. These findings support the hypothesis that individual Malassezia species may facilitate distinct patterns of cutaneous phenotype.