Division of Oral Molecular Microbiology, Department of Oral Pathobiological Science, Hokkaido University Graduate School of Dental Medicine, Kita 13, Nishi 7, Kita-ku, Sapporo 060-8586, Japan.
Cell Microbiol. 2012 Jan;14(1):40-57. doi: 10.1111/j.1462-5822.2011.01695.x. Epub 2011 Nov 3.
Dendritic cells recognize pathogens through pattern recognition receptors such as Toll-like receptors and phagocytose and digest them by phagocytic receptors for antigen presentation. This study was designed to clarify the cross-talk between recognition and phagocytosis of microbes in dendritic cells. The murine dendritic cell line XS106 cells were stimulated with the murine C-type lectin SIGNR1 ligand lipoarabinomannan and the Toll-like receptor 2 ligand FSL-1. The co-stimulation significantly suppressed FSL-1-mediated activation of NF-κB as well as production of TNF-α, IL-6 and IL-12p40 in a dose-dependent manner. The suppression was significantly but not completely recovered by knock-down of SIGNR1. SIGNR1 was associated with Toll-like receptor 2 in XS106 cells. The co-stimulation upregulated the expression of suppressor of cytokine signalling-1 in XS106 cells, the knock-down of which almost completely recovered the suppression of the FSL-1-mediated cytokine production by lipoarabinomannan. In addition, it was found that the MyD88-adaptor-like protein in XS106 cells was degraded by co-stimulation with FSL-1 and lipoarabinomannan in the absence, but not the presence, of the proteasome inhibitor MG132 and the degradation was inhibited by knock-down of suppressor of cytokine signalling-1. This study suggests that Toll-like receptor 2-mediated signalling is negatively regulated by SIGNR1-mediated signalling in dendritic cells, possibly through suppressor of cytokine signalling-1-mediated degradation of the MyD88-adaptor-like protein.
树突状细胞通过模式识别受体（如 Toll 样受体）识别病原体，并通过吞噬受体吞噬和消化它们，进行抗原呈递。本研究旨在阐明树突状细胞中微生物识别和吞噬的相互作用。用鼠 C 型凝集素 SIGNR1 配体脂阿拉伯甘露聚糖和 Toll 样受体 2 配体 FSL-1 刺激鼠树突状细胞系 XS106 细胞。共刺激显著抑制 FSL-1 介导的 NF-κB 的激活以及 TNF-α、IL-6 和 IL-12p40 的产生，呈剂量依赖性。通过 SIGNR1 的敲低，抑制作用得到显著但不完全的恢复。SIGNR1 与 XS106 细胞中的 Toll 样受体 2 相关。共刺激上调 XS106 细胞中细胞因子信号转导抑制物-1 的表达，其敲低几乎完全恢复脂阿拉伯甘露聚糖对 FSL-1 介导的细胞因子产生的抑制作用。此外，还发现 XS106 细胞中的 MyD88 衔接蛋白样蛋白在没有蛋白酶体抑制剂 MG132 的情况下，通过 FSL-1 和脂阿拉伯甘露聚糖的共刺激而降解，但在存在 MG132 的情况下不会降解，并且这种降解可以通过细胞因子信号转导抑制物-1 的敲低来抑制。本研究表明，Toll 样受体 2 介导的信号在树突状细胞中被 SIGNR1 介导的信号负调控，可能通过细胞因子信号转导抑制物-1 介导的 MyD88 衔接蛋白样蛋白的降解。
