The Skin Commensal Yeast Malassezia Triggers a Type 17 Response that Coordinates Anti-fungal Immunity and Exacerbates Skin Inflammation
Open accessAbstract
Commensal fungi of the mammalian skin, such as those of the genus Malassezia, are associated with atopic dermatitis and other common inflammatory skin disorders. Understanding of the causative relationship between fungal commensalism and disease manifestation remains incomplete. By developing a murine epicutaneous infection model, we found Malassezia spp. selectively induce IL-17 and related cytokines. This response is key in preventing fungal overgrowth on the skin, as disruption of the IL-23-IL-17 axis compromises Malassezia-specific cutaneous immunity. Under conditions of impaired skin integrity, mimicking a hallmark of atopic dermatitis, the presence of Malassezia dramatically aggravates cutaneous inflammation, which again was IL-23 and IL-17 dependent. Consistently, we found a CCR6+ Th17 subset of memory T cells to be Malassezia specific in both healthy individuals and atopic dermatitis patients, whereby the latter showed enhanced frequency of these cells. Thus, the Malassezia-induced type 17 response is pivotal in orchestrating antifungal immunity and in actively promoting skin inflammation.
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Type 3 ILCs are critical for anti-fungal defense in skin tissue.
“type 3 ILCs that are critical for anti-fungal defense in skin tissue (7).”
From Differential skin immune responses in mice intradermally infected with <i>Candida auris</i> and <i>Candida albicans</i> (2023) · cites this paper as [7]
C. auris enters the dermis and deeper tissues, including hair follicles, unlike other Candida species.
“Furthermore, C. auris not only colonizes the outer layer of the skin but also enters the dermis and deeper tissues, including hair follicles, a phenomenon that was not observed previously with other Candida species (4, 7).”
From Differential skin immune responses in mice intradermally infected with <i>Candida auris</i> and <i>Candida albicans</i> (2023) · cites this paper as [7]
IL-17+ T cell responses can promote tissue inflammatory diseases in predisposed hosts.
“It was suggested that while IL-17+ T cell responses are important in controlling commensal fungi or fungal pathogens, they can promote tissue inflammatory diseases in predisposed hosts.41,42,43”
From Skin-resident T cells play an important role in controlling skin colonization of Candidozyma (Candida) auris (2026) · cites this paper as [41]
IL-17+ T cell responses are important in controlling commensal fungi or fungal pathogens.
“It was suggested that while IL-17+ T cell responses are important in controlling commensal fungi or fungal pathogens, they can promote tissue inflammatory diseases in predisposed hosts.41,42,43”
From Skin-resident T cells play an important role in controlling skin colonization of Candidozyma (Candida) auris (2026) · cites this paper as [41]
IL-17-mediated immunity is central to mucocutaneous host defense against fungi such as C. albicans and Malassezia.
“IL-17-mediated immunity is central to mucocutaneous host defense against fungi such as C. albicans and Malassezia [10,99,100].”
From Host–Candida auris interactions in the skin (2026) · cites this paper as [10]
A deficiency in the CLR adaptor Card9 does not affect C. auris control in the skin, unlike its requirement for induction of Th17 cells during cutaneous Malassezia infection.
“In contrast to C. albicans, a deficiency in the CLR adaptor Card9, required for the induction of Th17 cells during cutaneous Malassezia infection [10,101,102], did not affect C. auris control in the skin [3].”
From Host–Candida auris interactions in the skin (2026) · cites this paper as [10]
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“Furthermore, C. auris not only colonizes the outer layer of the skin but also enters the dermis and deeper tissues, including hair follicles, a phenomenon that was not observed previously with other Candida species (4, 7).”
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Fungal gut microbiota dysbiosis in systemic lupus erythematosus
Yang, P., Xu, R. C., Chen, F., Chen, S., Khan, A., Li, L., Zhang, X., Wang, Y., Xu, Z., & Shen, H. (2023) · Frontiers in Microbiology · doi:10.3389/fmicb.2023.1149311 · Cited by 20 · see citing works
Li, L., Huang, X., & Chen, H. (2024) · Gut Microbes · doi:10.1080/19490976.2024.2328868 · Cited by 20 · see citing works
Prevalence of Malassezia species on the skin of HIV-seropositive patients
Krzyściak, P., Bakuła, Z., Gniadek, A., Garlicki, A., Tarnowski, M., Wichowski, M., & Jagielski, T. (2020) · Scientific Reports · doi:10.1038/s41598-020-74133-6 · Cited by 20 · see citing works
Microbial Components and Effector Molecules in T Helper Cell Differentiation and Function
Lee, C., Lee, H., Park, J. C., & Im, S. (2023) · Immune Network · doi:10.4110/in.2023.23.e7 · Cited by 19 · see citing works
Obesity and the microbiome in atopic dermatitis: Therapeutic implications for PPAR-γ agonists
McAleer, J. P. (2023) · Frontiers in Allergy · doi:10.3389/falgy.2023.1167800 · Cited by 19 · see citing works
Facial Redness in Atopic Dermatitis Patients Treated With Dupilumab: A Case Series
Seok, S. H., An, J. H., Shin, J. U., Lee, H. J., Kim, D. H., Yoon, M. S., & Kim, H. J. (2020) · Allergy Asthma and Immunology Research · doi:10.4168/aair.2020.12.6.1063 · Cited by 19 · see citing works
Torres, M., de Cock, H., & Ramírez, A. M. C. (2020) · Journal of Fungi · doi:10.3390/jof6030155 · Cited by 19 · see citing works
- Authors
- Sparber, F., De Gregorio, C., Steckholzer, S., Ferreira, F. M., Dolowschiak, T., Ruchti, F., Kirchner, F. R., Mertens, S., Prinz, I., Joller, N., Buch, T., Glatz, M., Sallusto, F., & LeibundGut-Landmann, S.
- Affiliations
- University of Zurich (CH)
- Medizinische Hochschule Hannover (DE)
- University Hospital Zurich (CH)
- ETH Zurich (CH)
- ORCID
- Venue
- Cell Host & Microbe
- Publisher
- Elsevier BV
- Published
- 2019-03
- Volume
- 25
- Issue
- 3
- Pages
- 389-403.e6
- ISSN
- 1931-3128 (ISSN-L)
- OpenAlex
- W2922478983
- Cited by
- 255
- References
- 84
- Citations by year
- 2026: 28 · 2025: 46 · 2024: 44 · 2023: 36 · 2022: 27 · 2021: 20 · 2020: 39 · 2019: 14
- FWCI
- 25.23
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Host & Microbe (publishedVersion)
- PubMed (publishedVersion)
- Zurich Open Repository and Archive (University of Zurich) (acceptedVersion)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion)
- Zurich Open Repository and Archive (University of Zurich)
- Funders
- University of Zürich
- European Research Council (323183, 677200)
- Helmut Horten Foundation
- Forschungskredit of the University of Zurich (FK-17-044)
- Swiss National Science Foundation (PP00P3_150663)
- Swiss Multiple Sclerosis Society
- Hertie Foundation (P1150013)
- Topics
- Health Sciences › Medicine › Dermatology › Dermatology and Skin Diseases
- Health Sciences › Medicine › Epidemiology › Nail Diseases and Treatments
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Keywords
- Malassezia, commensal fungi, atopic dermatitis, IL-17, IL-23, Th17 cells, CCR6, antifungal immunity, skin inflammation, skin barrier integrity, skin immunity
- MeSH terms
- Adult, Animals, Dermatitis, Atopic, Dermatomycoses, Disease Models, Animal, Female, Humans, Malassezia, Male, Mice, Inbred C57BL, Middle Aged, Cytokines, Young Adult, Th17 Cells
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