Differential dendritic cell responses to cell wall mannan of Candida albicans, Candida parapsilosis, and Candida dubliniensis

Mannan (mannosylated glycoproteins) in the outermost layer of the Candida cell wall may be the first molecules that interact with host dendritic cells (DCs) and activate immune responses that determine disease outcomes. However, little is known about how different mannan structures of common oral Candida species affect DC activation. The effects of heat-inactivated (HI) yeast cells and soluble mannan of Candida albicans, Candida parapsilosis, and Candida dubliniensis on bone marrow-derived DC (BMDC) responses were compared. HI Candida and the mannan exhibited different effects on BMDC activation and functions, which could be due to other carbohydrate compositions in the yeast cell wall. Among Candida mannan, the C. albicans mannan was the weakest stimulus and induced only interferon (IFN)-gamma production. This suggests the possibility that C. albicans mannan may skew T helper (Th) responses from protective Th17 toward Th1. In contrast, C. parapsilosis mannan caused strong BMDC activation and high production of several proinflammatory cytokines which possibly promote hyperinflammation. Meanwhile, C. dubliniensis mannan induced moderate BMDC responses, which may correlate with its lower pathogenicity. Therefore, mannan of each Candida species play distinct roles in DC responses and may be involved in the immunopathogenesis and disease severity of oral candidiasis as well as other Candida infection.