Malassezia yeasts activate the NLRP3 inflammasome in antigen-presenting cells via Syk-kinase signalling

Exp Dermatol. 2014 Dec;23(12):884-9. doi: 10.1111/exd.12552.

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.

Keywords: IL-1β; Malassezia; Syk; inflammasome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen-Presenting Cells / immunology*
  • Antigen-Presenting Cells / metabolism
  • Antigen-Presenting Cells / microbiology*
  • Carrier Proteins / genetics
  • Carrier Proteins / immunology*
  • Caspase 1 / metabolism
  • Cells, Cultured
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Dendritic Cells / microbiology
  • Dermatomycoses / immunology
  • Dermatomycoses / metabolism
  • Dermatomycoses / microbiology
  • Humans
  • Immunity, Innate
  • Inflammasomes / immunology*
  • Inflammasomes / metabolism
  • Interleukin-1beta / metabolism
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Lectins, C-Type / metabolism
  • Malassezia / genetics
  • Malassezia / immunology*
  • Malassezia / pathogenicity
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Molecular Sequence Data
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Protein-Tyrosine Kinases / metabolism*
  • Signal Transduction
  • Syk Kinase

Substances

  • CLEC7A protein, human
  • Carrier Proteins
  • Inflammasomes
  • Interleukin-1beta
  • Intracellular Signaling Peptides and Proteins
  • Lectins, C-Type
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • NLRP3 protein, human
  • Nlrp3 protein, mouse
  • Protein-Tyrosine Kinases
  • SYK protein, human
  • Syk Kinase
  • Syk protein, mouse
  • Caspase 1

Associated data

  • GENBANK/KM272586
  • GENBANK/KM272587
  • GENBANK/KM272588