Staged development of long-lived T-cell receptor αβ T H 17 resident memory T-cell population to Candida albicans after skin infection

摘要

BackgroundCandida albicansis a dimorphic fungus to which human subjects are exposed early in life, and by adulthood, it is part of the mycobiome of skin and other tissues. Neonatal skin lacks resident memory T (TRM) cells, but in adults theC燼lbicansskin test is a surrogate for immunocompetence. Young adult mice raised under specific pathogen-free conditions are naive toC albicansand have been shown recently to have an immune system resembling that of neonatal human subjects.ObjectiveWe studied the evolution of the adaptive cutaneous immune response toCandidaspecies.MethodsWe examined both human skin T cells and thede novoand memory immune responses in a mouse model ofC albicansskin infection.ResultsIn mice the initial IL-17producing cells afterC albicansinfection were dermal 炒 T cells, but by day 7, 辈 TH17 effector T cells were predominant. By day 30, the majority ofC albicansreactive IL-17producing T cells were CD4 TRMcells. Intravital microscopy showed that CD4 effector T cells were recruited to the site of primary infection and were highly motile 10燿ays after infection. Between 30 and 90燿ays after infection, these CD4 T cells became increasingly sessile, acquired expression of CD69 and CD103, and localized to the papillary dermis. These established TRMcells produced IL-17 on challenge, whereas motile migratory memory T cells did not. TRMcells rapidly clear an infectious challenge withC albicansmore effectively than recirculating T cells, although both populations participate. We found that in normal human skin IL-17producing CD4+TRMcells that responded toC albicansin an MHC class IIrestricted fashion could be identified readily.ConclusionsThese studies demonstrate thatC albicansinfection of skin preferentially generates CD4+IL-17producing TRMcells, which mediate durable protective immunity.