Subcellular localization of toll-like receptor 3 in human dendritic cells
Subcellular localization of toll-like receptor 3 in human dendritic cells
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DOI：
10.4049/jimmunol.171.6.3154
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发表时间：
2003-09-15
影响因子：
4.4
通讯作者：
Seya, T
中科院分区：
文献类型：
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作者：
Matsumoto, M;Funami, K;Seya, T
Toll 样受体 (TLR)3 识别 dsRNA 并转导信号以激活 NF-κB 和 IFN-β 启动子。 I 型干扰素 (IFN-α/β) 在抗病毒宿主防御中发挥关键细胞因子的作用。人成纤维细胞在细胞表面表达 TLR3，抗 TLR3 mAb 抑制 dsRNA 诱导的成纤维细胞分泌 IFN-β，表明 TLR3 作用于细胞表面来感知病毒感染。在本研究中，我们使用抗 TLR3 mAb 检查了人 TLR3 在各种 DC 亚群中的表达和定位。在单核细胞衍生的未成熟树突状细胞 (iDC) 中，TLR3 主要驻留在细胞内部，而不是细胞表面。 iDC 响应聚 (I:C) 产生 IL-12p70 以及 IFN-α 和 β。在用轮状病毒衍生的 dsRNA 处理的 iDC 中观察到类似的反应。这些反应不能通过用抗 TLR3 mAb 预处理细胞来阻断。在 CD11c(+) 血液 DC 中，与单核细胞来源的 iDC 中一样，也观察到 TLR3 的细胞质保留，再次证实了与成纤维细胞不同的 TLR3 分布谱。然而，在前体 DC2 中，在细胞内部或外部都无法检测到 TLR3。值得注意的是，有一种假定的中心体蛋白与骨髓 DC 和前体 DC2 中的 TLR3 共享一个表位，但与外周血单核细胞中的 TLR3 不共享表位。 Immunoelectron microscopic analysis revealed that TLR3, when stably expressed in the murine B cell line Ba/F3, was specifically accumulated in multivesicular bodies, a subcellular compartment situated in endocytic trafficking pathways.因此，TLR3的调节和定位在每种细胞类型中是不同的，这可能反映了细胞类型特异性的多种途径通过TLR3参与抗病毒IFN诱导。
Toll-like receptor (TLR)3 recognizes dsRNA and transduces signals to activate NF-kappaB and IFN-beta promoter. Type I IFNs (IFN-alpha/beta) function as key cytokines in anti-viral host defense. Human fibroblasts express TLR3 on the cell surface, and anti-TLR3 mAb inhibits dsRNA-induced IFN-beta secretion by fibroblasts, suggesting that TLR3 acts on the cell surface to sense viral infection. In this study, we examined the expression and localization of human TLR3 in various DC subsets using anti-TLR3 mAb. In monocyte-derived immature dendritic cells (iDCs), TLR3 predominantly resided inside the cells but not on the cell surface. iDCs produced IL-12p70 and IFN-alpha and -beta in response to poly(I:C). Similar response was observed in iDCs treated with rotavirus-derived dsRNA. These responses could not be blocked by pretreatment of the cells with anti-TLR3 mAb. In CD11c(+) blood DCs, cytoplasmic retention of TLR3 was also observed as in monocyte-derived iDCs, again endorsing a different TLR3 distribution profile from fibroblasts. In precursor DC2, however, TLR3 could not be detected inside or outside the cells. Of note, there was a putative centrosomal protein that shared an epitope with TLR3 in myeloid DCs and precursor DC2, but not peripheral blood monocytes. Immunoelectron microscopic analysis revealed that TLR3, when stably expressed in the murine B cell line Ba/F3, was specifically accumulated in multivesicular bodies, a subcellular compartment situated in endocytic trafficking pathways. Thus, regulation and localization of TLR3 are different in each cell type, which may reflect participation of cell type-specific multiple pathways in antiviral IFN induction via TLR3.