Properties regulating the nature of the plasmacytoid dendritic cell response to Toll-like receptor 9 activation.
Properties regulating the nature of the plasmacytoid dendritic cell response to Toll-like receptor 9 activation.
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DOI：
10.1084/jem.20060401
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发表时间：
2006-08-07
期刊：
影响因子：
--
通讯作者：
Barrat FJ
中科院分区：
文献类型：
--
作者：
Guiducci C;Ott G;Chan JH;Damon E;Calacsan C;Matray T;Lee KD;Coffman RL;Barrat FJ
人浆细胞类动物树突状细胞（PDC）可以产生干扰素（IFN）-α和/或成熟，并参与适应性免疫响应。刺激PDC的IFN-α产生和成熟的能力。 CpG寡核苷酸。多聚体CPG-A激活Transrin受体（TFR） - 阳性内体发生，并专门导致IFN-α产生阳性内体并促进PDC的成熟。 PDC，而CPG-A的单体形式将IFN-α产生的损失和PDC成熟活性的增益来实现的LAMP-1-1-阳性内体。在两种类型的内体中分布。 TLR9信号传导不是价值，而是内体位置，并且证明了对PDC中TLR9激活的生物学反应的严格分隔。
Human plasmacytoid dendritic cells (PDCs) can produce interferon (IFN)-α and/or mature and participate in the adaptive immune response. Three classes of CpG oligonucleotide ligands for Toll-like receptor (TLR)9 can be distinguished by different sequence motifs and different abilities to stimulate IFN-α production and maturation of PDCs. We show that the nature of the PDC response is determined by the higher order structure and endosomal location of the CpG oligonucleotide. Activation of TLR9 by the multimeric CpG-A occurs in transferrin receptor (TfR)-positive endosomes and leads exclusively to IFN-α production, whereas monomeric CpG-B oligonucleotides localize to lysosome-associated membrane protein (LAMP)-1–positive endosomes and promote maturation of PDCs. However, CpG-B, when complexed into microparticles, localizes in TfR-positive endosomes and induces IFN-α from PDCs, whereas monomeric forms of CpG-A localize to LAMP-1–positive endosomes accompanied by the loss of IFN-α production and a gain in PDC maturation activity. CpG-C sequences, which induce both IFN-α and maturation of PDCs, are distributed in both type of endosomes. Encapsulation of CpG-C in liposomes stable above pH 5.75 completely abrogated the IFN-α response while increasing PDC maturation. This establishes that the primary determinant of TLR9 signaling is not valency but endosomal location and demonstrates a strict compartmentalization of the biological response to TLR9 activation in PDCs.
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