Abstract
Malassezia sympodialis is a dominant commensal fungi in the human skin mycobiome but is also associated with common skin disorders including atopic eczema (AE). M. sympodialis releases extracellular vesicles, designated MalaEx, which are carriers of small RNAs and allergens, and they can induce inflammatory cytokine responses. Here we explored how MalaEx are involved in host-microbe interactions by comparing protein content of MalaEx with that of the parental yeast cells, and by investigating interactions of MalaEx with cells in the skin. Cryo-electron tomography revealed a heterogeneous population of MalaEx. iTRAQ based quantitative proteomics identified in total 2439 proteins in all replicates of which 110 were enriched in MalaEx compared to the yeast cells. Among the MalaEx enriched proteins were two of the M. sympodialis allergens, Mala s 1 and s 7. Functional experiments indicated an active binding and internalization of MalaEx into human keratinocytes and monocytes, and MalaEx were found in close proximity of the nuclei using super-resolution fluorescence 3D-SIM imaging. Our results provides new insights into host-microbe interactions, supporting that MalaEx may have a role in the sensitization and maintenance of inflammation in AE by containing enriched amounts of allergens and with their ability to interact with skin cells.
Highlights
Malassezia sympodialis is a dominant commensal fungi in the human skin mycobiome but is associated with common skin disorders including atopic eczema (AE)
We demonstrated that MalaEx are carriers of allergens[8], like human dendritic or B cell-derived exosomes[17,18], and can induce inflammatory cytokine responses with a significantly higher IL-4 production in peripheral blood mononuclear cells (PBMC) from patients with AE compared to healthy controls[8], supporting the link between AE and M. sympodialis
For proteomics we used MalaEx produced by M. sympodialis cultured for 72 h in mDixon broth to avoid contamination from fetal calf serum within the RPMI medium, which otherwise overrides the signals of less abundant proteins
Summary
Malassezia sympodialis is a dominant commensal fungi in the human skin mycobiome but is associated with common skin disorders including atopic eczema (AE). M. sympodialis releases extracellular vesicles, designated MalaEx, which are carriers of small RNAs and allergens, and they can induce inflammatory cytokine responses. Various types of EV ranging in size from 20 nm to 1,000 nm in diameter have been described and are classified mainly on their mechanisms of biogenesis and their physiological functions[10,15] Those designated exosomes have been shown to be involved in immunoregulatory mechanisms such as immune activation and suppression, and intercellular communication[15], whereas EV from microorganisms with thick cell walls, such as fungi, have been related to cytotoxicity, the invasion of host cells, and the transfer of virulence factors[11]. Cryo-electron tomography was used to visualize MalaEx’s morphology, and possible interactions between MalaEx and cells in the skin were investigated to further explore MalaEx’s role in host-microbe interactions
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