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首页> 外文期刊>Infection and immunity >Distinct Patterns of Dendritic Cell Cytokine Release Stimulated by Fungal β-Glucans and Toll-Like Receptor Agonists
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Distinct Patterns of Dendritic Cell Cytokine Release Stimulated by Fungal β-Glucans and Toll-Like Receptor Agonists

机译：真菌β-葡聚糖和Toll样受体激动剂刺激的树突状细胞细胞因子释放的不同模式

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β-Glucans derived from fungal cell walls have potential uses as immunomodulating agents and vaccine adjuvants. Yeast glucan particles (YGPs) are highly purified Saccharomyces cerevisiae cell walls composed of β1,6-branched β1,3-d-glucan and free of mannans. YGPs stimulated secretion of the proinflammatory cytokine tumor necrosis factor alpha (TNF-α) in wild-type murine bone marrow-derived myeloid dendritic cells (BMDCs) but did not stimulate interleukin-12p70 (IL-12p70) production. A purified soluble β1,6-branched β1,3-d-glucan, scleroglucan, also stimulated TNF-α in BMDCs. These two β-glucans failed to stimulate TNF-α in Dectin-1 (β-glucan receptor) knockout BMDCs. Costimulation of wild-type BMDCs with β-glucans and specific Toll-like receptor (TLR) ligands resulted in greatly enhanced TNF-α production but decreased IL-12p70 production compared with TLR agonists alone. The upregulation of TNF-α and downregulation of IL-12p70 required Dectin-1, but not IL-10. Gamma interferon (IFN-γ) priming did not overcome IL-12p70 reduction by β-glucans. Similar patterns of cytokine regulation were observed in human monocyte-derived dendritic cells (DCs) costimulated with YGPs and the TLR4 ligand lipopolysaccharide. Finally, costimulation of BMDCs with YGPs and either the TLR9 ligand, CpG, or the TLR2/1 ligand, Pam3CSK4, resulted in upregulated secretion of IL-1α and IL-10 and downregulated secretion of IL-1β, IL-6, and IFN-γ-inducible protein 10 but had no significant effects on IL-12p40, keratinocyte-derived chemokine, monocyte chemotactic protein 1, or macrophage inflammatory protein α, compared with the TLR ligand alone. Thus, β-glucans have distinct effects on cytokine responses following DC stimulation with different TLR agonists. These patterns of response might contribute to the skewing of immune responses during mycotic infections and have implications for the design of immunomodulators and vaccines containing β-glucans.
机译：源自真菌细胞壁的β-葡聚糖具有潜在用途，可作为免疫调节剂和疫苗佐剂。酵母葡聚糖颗粒（YGPs）是高度纯化的啤酒酵母细胞壁，由β1,6-支化的β1,3-d-葡聚糖组成，不含甘露聚糖。 YGP刺激野生型鼠源性骨髓树突状细胞（BMDCs）中促炎性细胞因子肿瘤坏死因子α（TNF-α）的分泌，但不刺激白介素12p70（IL-12p70）的产生。纯化的可溶性β1，6-支链β1，3-d-葡聚糖，硬葡聚糖也刺激了BMDC中的TNF-α。这两种β-葡聚糖不能刺激Dectin-1（β-葡聚糖受体）基因敲除的BMDC中的TNF-α。与单独的TLR激动剂相比，β-葡聚糖和特定的Toll样受体（TLR）配体对野生型BMDC的共刺激导致TNF-α的产生大大增强，但IL-12p70的产生却降低了。 TNF-α的上调和IL-12p70的下调需要Dectin-1，但不需要IL-10。 γ干扰素（IFN-γ）引发不能克服β-葡聚糖降低IL-12p70的作用。在与YGP和TLR4配体脂多糖共刺激的人单核细胞衍生树突细胞（DC）中观察到相似的细胞因子调节模式。最后，与YGP和TLR9配体CpG或TLR2 / 1配体Pam 3 CSK 4 共同刺激BMDC，导致IL-1α和IL-10与IL-1β，IL-6和IFN-γ诱导蛋白10的分泌下调，但对IL-12p40，角质形成细胞趋化因子，单核细胞趋化蛋白1或巨噬细胞炎性蛋白α没有明显影响。单独使用TLR配体。因此，在使用不同的TLR激动剂进行DC刺激后，β-葡聚糖对细胞因子的反应具有明显的影响。这些反应模式可能有助于霉菌感染期间免疫反应的倾斜，并且对包含β-葡聚糖的免疫调节剂和疫苗的设计有影响。

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