Sahasrabudhe Neha M, Dokter-Fokkens Jelleke, de Vos Paul
Immunoendocrinology, Division of Medical Biology, Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Mol Nutr Food Res. 2016 Nov;60(11):2514-2522. doi: 10.1002/mnfr.201600356. Epub 2016 Aug 11.
The major receptor for β(1-3)-glucans on immune cells is considered to be Dectin-1 receptor. Particulate β-glucans induce stronger immune responses than soluble β-glucans by clustering of Dectin-1 receptors. Here, it was hypothesized that activation of other pattern recognition receptors such as Toll-like receptor 4 (TLR4) can also contribute to enhanced activity of immune cells after exposure to particulate β-glucans.
To test this hypothesis, reporter cell lines were designed expressing TLR4 with either Dectin-1A or Dectin-1B, that is, one of the two transcript variants of human Dectin-1 receptors. Enhanced NF-κB activation was observed after stimulation with particulate β-glucans in both Dectin-1A-TLR4 and the Dectin-1B-TLR4 cell lines. This was different with soluble β-glucans, which enhanced activation in Dectin-1A-TLR4 cell lines but not in Dectin-1B-TLR4 cells. The synergistic activation of TLR4 and Dectin-1 by particulate β-glucans was confirmed in human dendritic cells. The effects of particulate β-glucan induced TLR4 binding were regulatory as blocking TLR4 enhanced pro-inflammatory cytokine IL-23, IL-4, IL-6, and TNF-α production.
These results suggest that TLR4 and Dectin-1 are synergistically activated by particulate β-glucans, wherein TLR4 activates an immune regulatory pathway in human dendritic cells. Our data suggest that β-glucan is an immune regulatory ligand for TLR4.
免疫细胞上β(1-3)-葡聚糖的主要受体被认为是脱噬素-1受体。颗粒状β-葡聚糖通过脱噬素-1受体的聚集诱导比可溶性β-葡聚糖更强的免疫反应。在此，有人提出假设，其他模式识别受体如Toll样受体4（TLR4）的激活也可能有助于颗粒状β-葡聚糖暴露后免疫细胞活性的增强。
为了验证这一假设，设计了报告细胞系，表达带有脱噬素-1A或脱噬素-1B的TLR4，脱噬素-1A或脱噬素-1B即人类脱噬素-1受体的两种转录变体之一。在颗粒状β-葡聚糖刺激后，脱噬素-1A-TLR4和脱噬素-1B-TLR4细胞系中均观察到NF-κB激活增强。可溶性β-葡聚糖的情况则不同，它能增强脱噬素-1A-TLR4细胞系中的激活，但不能增强脱噬素-1B-TLR4细胞中的激活。颗粒状β-葡聚糖对TLR4和脱噬素-1的协同激活在人树突状细胞中得到证实。颗粒状β-葡聚糖诱导的TLR4结合的作用具有调节性，因为阻断TLR4会增强促炎细胞因子IL-23、IL-4、IL-6和TNF-α的产生。
这些结果表明，颗粒状β-葡聚糖可协同激活TLR4和脱噬素-1，其中TLR4在人树突状细胞中激活一条免疫调节途径。我们的数据表明β-葡聚糖是TLR4的一种免疫调节配体。
