title: Malassezia yeasts activate the NLRP3 inflammasome in antigen-presenting cells via Syk-kinase signalling.
abstract: Although being a normal part of the skin flora, yeasts of the genus Malassezia are associated with several common dermatologic conditions including pityriasis versicolour, seborrhoeic dermatitis (SD), folliculitis, atopic eczema/dermatitis (AE/AD) and dandruff. While Malassezia spp. are aetiological agents of pityriasis versicolour, a causal role of Malassezia spp. in AE/AD and SD remains to be established. Previous reports have shown that fungi such as Candida albicans and Aspergillus fumigatus are able to efficiently activate the NLRP3 inflammasome leading to robust secretion of the pro-inflammatory cytokine IL-1β. To date, innate immune responses to Malassezia spp. are not well characterized. Here, we show that different Malassezia species could induce NLRP3 inflammasome activation and subsequent IL-1β secretion in human antigen-presenting cells. In contrast, keratinocytes were not able to secrete IL-1β when exposed to Malassezia spp. Moreover, we demonstrate that IL-1β secretion in antigen-presenting cells was dependent on Syk-kinase signalling. Our results identify Malassezia spp. as potential strong inducers of pro-inflammatory responses when taken up by antigen-presenting cells and identify C-type lectin receptors and the NLRP3 inflammasome as crucial actors in this process.
authors.affiliation: Department of Dermatology, University Hospital, Zürich, Switzerland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Kistowska
authors.forename: Gabriele
authors.initials: G
authors.lastname: Fenini
authors.forename: Dragana
authors.initials: D
authors.lastname: Jankovic
authors.forename: Laurence
authors.initials: L
authors.lastname: Feldmeyer
authors.forename: Katrin
authors.initials: K
authors.lastname: Kerl
authors.forename: Philipp
authors.initials: P
authors.lastname: Bosshard
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Contassot
authors.forename: Lars E
authors.initials: LE
authors.lastname: French
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology*; D020170:Caspase 1 / Q000378:metabolism; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D003881:Dermatomycoses / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D006801:Humans; D007113:Immunity, Innate; D058847:Inflammasomes / Q000276:immunology* / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D037181:Lectins, C-Type / Q000378:metabolism; D008290:Malassezia / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D015398:Signal Transduction; D000072377:Syk Kinase; D000099181:Dectin-1
chemical_list: D002352:Carrier Proteins; D020170:Caspase 1; D058847:Inflammasomes; D053583:Interleukin-1beta; D047908:Intracellular Signaling Peptides and Proteins; D037181:Lectins, C-Type; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D011505:Protein-Tyrosine Kinases; D000072377:Syk Kinase; C546929:CLEC7A protein, human; D000099181:Dectin-1; C453881:NLRP3 protein, human; C492716:Nlrp3 protein, mouse; C000606896:SYK protein, human; C000606897:Syk protein, mouse
keywords: IL-1β; Malassezia; Syk; inflammasome