Card9 and MyD88 differentially regulate Th17 immunity to the commensal yeastMalasseziain the murine skin

Abstract

ABSTRACTThe fungal community of the skin microbiome is dominated by a single genus,Malassezia. Besides its symbiotic lifestyle at the host interface, this commensal yeast has also been associated with diverse inflammatory skin diseases in humans and pet animals. Stable colonization is maintained by antifungal type 17 immunity. The mechanisms driving Th17 responses toMalasseziaremain, however, unclear. Here, we show that the C-type lectin receptors Mincle, Dectin-1, and Dectin-2 recognize conserved patterns in the cell wall ofMalasseziaand induce dendritic cell activationin vitro, while only Dectin-2 is required for Th17 activation during experimental skin colonizationin vivo.In contrast, Toll-like receptor recognition was redundant in this context. Instead, inflammatory IL-1 family cytokines signaling via MyD88 were also implicated in Th17 activation in a T cell-intrinsic manner. Taken together, we characterized the pathways contributing to protective immunity against the most abundant member of the skin mycobiome. This knowledge contributes to the understanding of barrier immunity and its regulation by commensals and is relevant considering how aberrant immune responses are associated with severe skin pathologies.