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γδ T cells respond directly and selectively to the skin commensal yeast Malassezia for IL-17-dependent fungal control.
- Source :
- PLoS Pathogens; 1/12/2024, Vol. 20 Issue 1, p1-27, 27p
- Publication Year :
- 2024
-
Abstract
- Stable microbial colonization of the skin depends on tight control by the host immune system. The lipid-dependent yeast Malassezia typically colonizes skin as a harmless commensal and is subject to host type 17 immunosurveillance, but this fungus has also been associated with diverse skin pathologies in both humans and animals. Using a murine model of Malassezia exposure, we show that Vγ4<superscript>+</superscript> dermal γδ T cells expand rapidly and are the major source of IL-17A mediating fungal control in colonized skin. A pool of memory-like Malassezia-responsive Vγ4<superscript>+</superscript> T cells persisted in the skin, were enriched in draining lymph nodes even after fungal clearance, and were protective upon fungal re-exposure up to several weeks later. Induction of γδT17 immunity depended on IL-23 and IL-1 family cytokine signalling, whereas Toll-like and C-type lectin receptors were dispensable. Furthermore, Vγ4<superscript>+</superscript> T cells from Malassezia-exposed hosts were able to respond directly and selectively to Malassezia-derived ligands, independently of antigen-presenting host cells. The fungal moieties detected were shared across diverse species of the Malassezia genus, but not conserved in other Basidiomycota or Ascomycota. These data provide novel mechanistic insight into the induction and maintenance of type 17 immunosurveillance of skin commensal colonization that has significant implications for cutaneous health. Author summary: Malassezia is the most abundant fungus living on our skin and is usually harmless, but this microbe has also been shown to play a role in pathological conditions such as eczema and dermatitis. Here, we investigated how a population of Vγ4<superscript>+</superscript> γδ T cells protect mouse skin against fungal overgrowth. While generally considered part of the innate immune system, we found that γδ T cells were maintained long after Malassezia was cleared from the skin of experimentally-infected animals. These cells displayed memory-like features and were highly efficient at fighting the fungus after a secondary challenge. We observed that classic fungal pattern recognition receptors were not involved, and that antigen-presenting cells were not required to generate Malassezia-protective γδ T cells. Finally, we confirmed that murine γδ T cells can directly recognise Malassezia and that the Malassezia-derived structure that triggers these responses was not conserved among other fungi. Our results highlight for the first time an important role for γδ T cells in preventing uncontrolled growth of the most abundant skin fungus. These findings have implications for several Malassezia-associated pathologies including eczema, dermatitis, and potentially even cancer. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 15537366
- Volume :
- 20
- Issue :
- 1
- Database :
- Complementary Index
- Journal :
- PLoS Pathogens
- Publication Type :
- Academic Journal
- Accession number :
- 174784551
- Full Text :
- https://doi.org/10.1371/journal.ppat.1011668