Candida albicans morphology and dendritic cell subsets determine T helper cell differentiation

Candida albicans is a dimorphic fungus responsible for chronic mucocutaneous and systemic infections.Mucocutaneous immunity to C.albicans requires Thelper 17 (Th17) cell differentiation that is thought to depend on recognition of filamentous C.albicans. Systemic immunity is considered Tcell independent. Using a murine skin infection model, we compared T helper cell responses to yeast and filamentous C.albicans. We found that only yeast induced Th17 cell responses through a mechanism that required Dectin-1-mediated expression of interleukin-6 (IL-6) by Langerhans cells. Filamentous forms induced Th1 without Th17 cell responses due to the absence of Dectin-1 ligation. Notably, Th17 cell responses provided protection against cutaneous infection while Th1 cell responses providedprotection against systemic infection. Thus, C.albicans morphology drives distinct T helper cell responses that provide tissue-specific protection. These findings provide insight into compartmentalization of Th cell responses and C.albicans pathogenesis and have critical implications for vaccine strategies.