Abstract:
Mannan in the outermost layer of 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 how different mannan structures of common Candida species affect DC activation and T cell responses. Thus, this work compared the effects of mannans of Candida albicans, Candida tropicalis, Candida glabrata, Candida krusei, Candida parapsilosis and Candida dubliniensis on bone marrow-derived DC (BMDC) responses in mice. C. albicans and C. tropicalis mannan could not activate DC maturation, however, they induced IFN-gamma production which consequently provoked Th1 responses. C. glabrata mannan potentially induced DC maturation, but it failed to mediate the cytokine production. In contrast, C. parapsilosis mannan caused strong DC activation and high production of several pro-inflammatory cytokines which possibly promote hyperinflammation. Meanwhile, C. dubliniensis mannan induced moderate BMDC responses, which may correlate with its lower pathogenicity. Cell wall mannan of C. albicans, C. tropicalis, C. glabrata, C. parapsilosis and C. dubliniensis had no effect on DC viability. Interestingly, C. krusei mannan triggered the massive production of pro-inflammatory cytokines in DCs, and this high activation state of DCs consequently leaded to the cellular apoptosis. The induction of DC apoptosis upon C. krusei mannan was mediated via TLR2- and MyD88 pathway. Although DCs underwent apoptosis upon C. krusei mannan stimulation, they were still capable of initiating T cells responses. In addition, the activation of MyD88 in DCs by C. krusei mannan controlled Th1/Th17 switching by virtue of the polarizing cytokines IL-12 and IL-6. The structure and composition of Candida cell wall mannan crucially promotes either host protective immunity or fungal immune evasion through differential activation of DCs. Therefore, mannan of each Candida species may be involved in the immunopathogenesis and disease severity of systemic and mucocutaneous candidiasis.
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