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Infecting Mice with Malassezia spp. to Study the Fungus-Host Interaction
Published on: November 6, 2019
[Role of Malassezia colonization in cutaneous immune response]
1Department of Immunobiology, Meiji Pharmaceutical University, Tokyo, Japan.
Abstract:
Malassezia yeasts are part of the cutaneous microflora and are also associated with a number of skin diseases such as pityriasis versicolor, seborrheic dermatitis, and atopic dermatitis (AD). Among organisms of the Malassezia species, M. globosa and M. restricta are highly associated with AD. However, their precise role in AD has remained uncertain. We first attempted to identify major allergens from M. globosa using a proteomics analysis. Immunoblotting showed that IgE-reactive components with molecular masses of 40-45 kDa proteins were detected by 100% (28 of 28) of sera from AD patients. The IgE-reactive allergens corresponding to the 42 kDa protein (MGp42) were identified by two-dimensional immunoblotting, and partially sequenced by MALDI-TOF MS with post source decay (PSD) of the peptide digest. Comparison of sequences with known protein sequences revealed that MGp42 showed similarity to the heat shock protein (hsp) family. Our studies have also demonstrated that human keratinocytes responded to the two Malassezia species with different Th2-type cytokine profiles, i.e. M. globosa induced IL-5, IL-10, and IL-13 secretion from the keratinocytes, whereas M. restricta induced IL-4 secretion. These findings suggest that M. globosa and M. restricta play a synergistic role in triggering or exacerbating AD by stimulating the Th2 immune response.
Insights
Malassezia yeasts, particularly M. globosa and M. restricta, are linked to atopic dermatitis (AD). These yeasts may trigger or worsen AD by stimulating immune responses, with M. globosa producing a 42 kDa heat shock protein allergen.
Area of Science:
- Dermatology
- Immunology
- Microbiology
Background:
- Malassezia yeasts are common skin microflora.
- Malassezia species, especially M. globosa and M. restricta, are associated with atopic dermatitis (AD).
- The exact role of Malassezia in AD pathogenesis is unclear.
Purpose of the Study:
- To identify major allergens from Malassezia globosa.
- To investigate the immune response of human keratinocytes to Malassezia globosa and M. restricta.
Main Methods:
- Proteomics analysis to identify allergens from M. globosa.
- Immunoblotting to detect IgE-reactive components in AD patient sera.
- Two-dimensional immunoblotting and MALDI-TOF MS for allergen identification and sequencing.
- Cytokine profiling of human keratinocytes stimulated with Malassezia species.
Main Results:
- A 42 kDa protein (MGp42) from M. globosa was identified as a major allergen, recognized by 100% of AD patient sera.
- MGp42 showed similarity to heat shock proteins.
- M. globosa induced IL-5, IL-10, and IL-13 secretion from keratinocytes.
- M. restricta induced IL-4 secretion from keratinocytes.
Conclusions:
- Malassezia globosa and M. restricta may synergistically contribute to triggering or exacerbating AD.
- These yeasts stimulate Th2-type immune responses, implicating them in AD pathogenesis.
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