Abstract
BackgroundDendritic cells capture antigens through PRRs and modulate adaptive immune responses. The type of adaptive immune T cell response generated is dependent upon the type of PRR activated by the microbes. Dectin-1 is a C-type lectin receptor present on dendritic cells.Methodology/Principal FindingsHere we show that selective dectin-1 agonist Curdlan can activate human DCs and induce the secretion of large amounts of IL-23, IL-1β, IL-6 and low levels of IL-12p70 as determined by ELISA. The Curdlan-stimulated DCs are efficient at priming naïve CD4 cells to differentiate into Th17 and Th1 cells. Furthermore, these CD4 T cells induce differentiation of B cells to secrete IgG and IgA. In addition, Curdlan-stimulated DCs promote the expansion and differentiation of Granzyme and perforin expressing cytotoxic T lymphocyte that display high cytolytic activity against target tumor cells in vitro.Conclusions/SignificanceThese data demonstrate that DCs stimulated through Dectin-1 can generate efficient Th, CTL and B cell responses and can therefore be used as effective mucosal and systemic adjuvants in humans.
Highlights
Cells of the innate immune system such as dendritic cells (DCs) detect and respond to pathogens through the expression of pattern recognition receptors (PRRs)
Our previous studies had shown that stimulation of DCs by Yeast cell wall Zymosan, a Toll-like receptors (TLRs) 2/6 and Dectin-1 stimulus polarized the CD4 T cell response towards T- regulatory type [14] while E.coli LPS, a TLR4 agonist polarized it towards Th1 type response [12]
Curdlan is a linear b-1, 3glucan of,500-mers derived from the bacterium Alcaligenes faecal. var. myxogenes We examined the activation of DCs in response to these stimuli
Summary
Cells of the innate immune system such as dendritic cells (DCs) detect and respond to pathogens through the expression of pattern recognition receptors (PRRs). Exposure of DCs to ligands of all these PRRs results in production of cytokines that modulate the type of T cell response and functions [1,7,8]. The nature of the cytokines produced by DCs in response to various ligands dictates the type of Th cell responses. Our previous studies have shown that engagement of different TLRs on DCs produces divergent type of adaptive immune responses. Dendritic cells capture antigens through PRRs and modulate adaptive immune responses. The type of adaptive immune T cell response generated is dependent upon the type of PRR activated by the microbes. Dectin-1 is a Ctype lectin receptor present on dendritic cells
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