γδ T cells respond directly and selectively to the skin commensal yeast Malassezia for IL-17-dependent fungal control.

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+ 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+ 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+ 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.

The skin mycobiome and intermicrobial interactions in the cutaneous niche.

Mammalian microbiomes have coevolved with their host to establish a stable homeostatic relationship. Multifaceted commensal-host and commensal-commensal interactions contribute to the maintenance of the equilibrium with an impact on diverse host physiological processes. Despite constant exposure to physical and chemical insults from the environment, the skin harbors a surprisingly stable microbiome. The fungal compartment of the skin microbiome, the skin mycobiome, is unique in that it is dominated by a single fungus, Malassezia. The lack in diversity suggests that the skin may provide a unique niche for this fungal genus and that Malassezia may efficiently outcompete other fungi from the skin. This opinion article examines aspects in support of this hypothesis, discusses how changes in niche conditions associate with skin mycobiome dysregulation, and highlights an emerging example of Malassezia being displaced from the skin by the emerging fungal pathogen C. auris, thereby generating a predisposing situation for fatal-invasive infection.