Staged development of long-lived T-cell receptor αβ TH17 resident memory T-cell population toCandida albicansafter skin infection

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Candida 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 albicansskin 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.


We studied the evolution of the adaptive cutaneous immune response toCandidaspecies.


We examined both human skin T cells and thede novoand memory immune responses in a mouse model ofC albicansskin infection.


In mice the initial IL-17–producing cells afterC albicansinfection were dermal γδ T cells, but by day 7, αβ TH17 effector T cells were predominant. By day 30, the majority ofC albicans–reactive IL-17–producing T cells were CD4 TRM cells. Intravital microscopy showed that CD4 effector T cells were recruited to the site of primary infection and were highly motile 10 days after infection. Between 30 and 90 days after infection, these CD4 T cells became increasingly sessile, acquired expression of CD69 and CD103, and localized to the papillary dermis. These established TRM cells produced IL-17 on challenge, whereas motile migratory memory T cells did not. TRM cells rapidly clear an infectious challenge withC albicansmore effectively than recirculating T cells, although both populations participate. We found that in normal human skin IL-17–producing CD4+ TRM cells that responded toC albicansin an MHC class II–restricted fashion could be identified readily.


These studies demonstrate thatC albicansinfection of skin preferentially generates CD4+ IL-17–producing TRM cells, which mediate durable protective immunity.

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