Department of Experimental Medicine and Biochemical Sciences, University of Perugia, 06126 Perugia, Italy
Abstract: In the past decade, a dramatic shift has occurred in our mechanistic understanding of immunity to fungi. It has became apparent that understanding how innate immune responses are activated will result in the construction of better vaccines and immunomodulatory strategies that are effective at eliciting protective immunity to fungi. The model has brought dendritic cells (DCs) to center stage as promising targets for immunotherapy intervention, and vaccine development and has shifted the emphasis from the "antigen" towards the "adjuvant". DCs function at three levels in the manipulation of the immune response to fungi. First, they mount an immediate or innate response to them by producing inflammatory mediators upon capture and phagocytosis; second, through these preceding innate functions, they decode the fungus-associated information and translate it in qualitatively different T helper (Th) responses, and third they have a key role in containing and dampening inflammatory responses by toler-ization through the induction of regulatory T cells (Treg). This chapter will highlight how the remarkable functional plasticity of DCs in response to fungi can be exploited for the deliberate targeting of cells and pathways of cell-mediated immunity in response to fungi and candidate fungal vaccines
Abbreviations: AEDS: atopic eczema/dermatitis syndrome; CRs: complement receptors; DCs: dendritic cells; CTLA-4: cytotoxic T lymphocyte antigen-4; FcR: Fc receptors; HSCT: hematopoietic stem cell transplantation; IDO: indoleamine 2,3-dioxygenase; IL: inter-leukin; lDCs: lymphoid dendritic cells; MAPK: mitogen-activated protein kinases; mDCs: myeloid dendritic cells; MHC: major histocompatibility complex; MR: mannose receptors; MyD88: Drosophila myeloid differentiation primary response gene 88; NK: natural killer cells; PAMPs: pathogen-associated molecular patterns; pDCs: plasma-cytoid dendritic cells; PKC: protein kinase C; PP: Payer's patches; PRRs: pattern recognition receptors; Th: T helper; Treg: regulatory T cells; TLRs: Toll-like receptors
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