Expression and function of Toll-like receptors on dendritic cells and other antigen presenting cells from non-human primates
Expression and function of Toll-like receptors on dendritic cells and other antigen presenting cells from non-human primates
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DOI：
10.1016/j.vetimm.2008.05.001
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发表时间：
2008-09-15
影响因子：
1.8
通讯作者：
Ruxrungtham, Kiat
中科院分区：
文献类型：
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作者：
Ketloy, Chutitorn;Engering, Anneke;Ruxrungtham, Kiat
抗原呈递细胞 (APC)，尤其是树突状细胞 (DC)，通过 Toll 样受体 (TLR) 感知微生物入侵，在针对感染的免疫反应中发挥着至关重要的作用。在这方面，TLR 配体是在人类和动物模型中用作疫苗佐剂的有吸引力的候选者。迄今为止，尚未对恒河猴等非人灵长类动物中的 TLR 表达进行研究。因此，我们研究了恒河猴不同 APC 亚群中的 TLR 表达模式，并将其与人类相似的 APC 亚群进行比较。此外，还将表达与来自小鼠不同器官的相应 DC 子集进行了比较。在这里，我们通过半定量 RT-PCR 表明，恒河猴的血液 DC 亚群表达了与人类相同的 TLR 组，但与小鼠 DC 亚群存在显着差异。猕猴髓样 DC (MDC) 表达 TLR3、4、7 和 8，而猕猴浆细胞样 DC (PDC) 仅表达 TLR7 和 9。此外，猕猴单核细胞衍生的树突细胞 (mo-DC)（即 TLR3、4、8 和 9）、单核细胞（即 TLR4、7 和 8）和 B 细胞中的 TLR 表达模式（即 TLR4、7、8 和 9）也与人类对应物相似。然而，猕猴 APC 对某些 TLR 配体的反应在表型分化和细胞因子产生方面与人类部分不同。引人注目的是，与人类 mo-DC 相比，当用 TLR 配体刺激猕猴 mo-DC 时，没有观察到 IL-12p70 的产生。此外，猕猴mo-DC对TLR8配体（poly U）的CD40和CD86表型反应高于人类。尽管存在这些功能差异，我们的结果为合理设计动物模型以评估 TLR 配体作为体内佐剂提供了重要信息。 (C) 2008 年由 Elsevier B.V. 出版
Antigen presenting cells (APCs), especially dendritic cells (DCs), play a crucial role in immune responses against infections by sensing microbial invasion through Toll-like receptors (TLRs). In this regard, TLR ligands are attractive candidates for use in humans and animal models as vaccine adjuvants. So far, no studies have been performed on TLR expression in non-human primates such as rhesus macaques. Therefore, we studied the TLR expression patterns in different subsets of APC in rhesus macaques and compared them to similar APC subsets in human. Also, expression was compared with corresponding DC subsets from different organs from mice. Here we show by semi-quantitative RT-PCR, that blood DC subsets of rhesus macaque expressed the same sets of TLRs as those of human but substantially differed from mouse DC subsets. Macaque myeloid DCs (MDCs) expressed TLR3, 4, 7 and 8 whereas macaque plasmacytoid DCs (PDCs) expressed only TLR7 and 9. Additionally, TLR expression patterns in macaque monocyte-derived dendritic cells (mo-DCs) (i.e., TLR3, 4, 8 and 9), monocytes (i.e., TLR4, 7, and 8) and B cells (i.e., TLR4, 7, 8, and 9) were also similar to their human counterparts. However, the responsiveness of macaque APCs to certain TLR ligands partially differed from that of human in terms of phenotype differentiation and cytokine production. Strikingly, in contrast to human mo-DCs, no IL-12p70 production was observed when macaque mo-DCs were stimulated with TLR ligands. In addition, CD40 and CD86 phenotypic responses to TLR8 ligand (poly U) in mo-DCs of macaque were higher than that of human. Despite these functional differences, our results provide important information for a rational design of animal models in evaluating TLR ligands as adjuvant in vivo. (C) 2008 Published by Elsevier B.V.