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首页> 外文期刊>Immunology: An Official Journal of the British Society for Immunology >CNL, a ricin B-like lectin from mushroom Clitocybe nebularis, induces maturation and activation of dendritic cells via the toll-like receptor 4 pathway.
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CNL, a ricin B-like lectin from mushroom Clitocybe nebularis, induces maturation and activation of dendritic cells via the toll-like receptor 4 pathway.

机译：CNL是一种来自蘑菇Clitocybe nebularis的蓖麻毒蛋白B样凝集素，可通过toll样受体4途径诱导树突状细胞成熟和激活。

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摘要

A novel lectin, isolated from the basidiomycete mushroom Clitocybe nebularis and termed C. nebularis lectin (CNL), exhibits an immunostimulatory effect on the most potent antigen-presenting cells, the dendritic cells (DCs). Treatment of human monocyte-derived DCs with CNL in doses from 1 to 10 mug/ml resulted in a dose-dependent induction of overall DC maturation characteristics. Exposure of DCs to CNL for 48 hr resulted in extensive up-regulation of co-stimulatory molecules CD80 and CD86, as well as of the maturation marker CD83 and HLA-DR molecules. Such CNL-matured DCs (CNL-DCs) were capable of inducing a T helper type 1-polarized response in naive CD4+ CD45RA+ T cells in 5-day allogeneic co-cultures. The allostimulatory potential of CNL-DCs was significantly increased relative to untreated controls, as was their capacity to produce several pro-inflammatory cytokines such as interleukin-6, interleukin-8 and tumour necrosis factor-alpha. By using a specific Toll-like receptor 4 (TLR4) signalling inhibitor, CLI-095, as well as Myd88 inhibitory peptide, we have shown that DC activation by CNL is completely dependent on the TLR4 activation pathway. Furthermore, activation of TLR4 by CNL was confirmed via TLR4 reporter assay. Measurement of p65 nuclear factor-kappaB and p38 mitogen-activated protein kinase (MAPK) phosphorylation levels following CNL stimulation of DCs revealed primarily an increase in nuclear factor-kappaB activity, with less effect on the induction of p38 MAPK signalling than of lipopolysaccharide-matured DCs. The CNL had the ability to activate human DCs in such a way as to subsequently direct T helper type 1 T-cell responses. Our results encourage the use of mushroom-derived lectins for use in therapeutic strategies with aims such as to strengthen anti-tumour immune responses.
机译：一种新的凝集素，是从担子菌蘑菇星状细胞中分离出来的，被称为星状梭菌凝集素（CNL），对最有效的抗原呈递细胞树突状细胞（DC）具有免疫刺激作用。用CNL处理人单核细胞衍生的DC，剂量为1至10杯/毫升，导致总DC成熟特性的剂量依赖性诱导。 DC暴露于CNL 48小时导致共刺激分子CD80和CD86以及成熟标记CD83和HLA-DR分子的大量上调。此类CNL成熟的DC（CNL-DC）能够在5天同种异体共培养的原始CD4 + CD45RA + T细胞中诱导T辅助型1极化反应。相对于未经处理的对照，CNL-DC的同种异体刺激潜力显着增加，它们产生几种促炎细胞因子（如白介素6，白介素8和肿瘤坏死因子-α）的能力也显着提高。通过使用特定的Toll样受体4（TLR4）信号抑制剂CLI-095和Myd88抑制肽，我们已经显示CNL的DC激活完全依赖于TLR4激活途径。此外，通过TLR4报告基因测定证实了CNL对TLR4的激活。 CNL刺激DC后测量p65核因子-kappaB和p38丝裂原激活的蛋白激酶（MAPK）磷酸化水平主要显示核因子-kappaB活性增加，对p38 MAPK信号传导的影响比脂多糖成熟的影响小DC。 CNL具有激活人类DC的能力，从而可以随后指导T辅助1型T细胞反应。我们的研究结果鼓励将蘑菇来源的凝集素用于治疗策略，以增强抗肿瘤免疫反应。

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