5 years ago

Staged development of long lived TCRαβ Th17 resident memory T cell population to Candida albicans after skin infection

Candida albicans is a dimorphic fungus to which humans 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 the C. albicans skin test is a surrogate for immunocompetence. Young adult mice raised under SPF conditions are naive to C. albicans, and have recently been shown to have an immune system resembling that of neonatal humans. Objective We studied the evolution of the adaptive cutaneous immune response to Candida. Methods We examined both human skin T cells and the de novo and memory immune responses in a mouse model of C. albicans skin infection. Results In mice, the initial IL-17 producing cells after C. albicans infection were dermal γδ T cells, but by day 7 αβ Th17 T effector cells were predominant. By day 30, the majority of C. 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 post infection. Between 30-90 days post infection, these CD4 T cells became increasingly sessile, acquired expression of CD69 and CD103, and localized to the papillary dermis. These established TRM produced IL-17 upon challenge, while motile migratory memory T (TMM) cells did not. TRM rapidly clear an infectious challenge with C. albicans more effectively than re-circulating T cells, though both populations participate. We found that in normal human skin, IL-17 producing CD4+ TRM that responded to C. albicans in an MHC Class II restricted fashion could be readily identified. Conclusions These studies demonstrate that C. albicans infection of skin preferentially generates CD4+ IL-17 producing TRM, which mediate durable protective immunity.


Candida albicans infection of skin preferentially generates TCRαβ Th17 resident memory T cells, which mediate protective immunity to C. albicans.

Publisher URL: www.sciencedirect.com/science

DOI: S0091674917317372

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