Transcriptomal signatures of vaccine adjuvants and accessory immunostimulation of sentinel cells by toll-like receptor 2/6 agonists
Transcriptomal signatures of vaccine adjuvants and accessory immunostimulation of sentinel cells by toll-like receptor 2/6 agonists
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DOI：
10.1080/21645515.2018.1480284
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发表时间：
2018-01-01
影响因子：
4.8
通讯作者：
David, Sunil A.
中科院分区：
文献类型：
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作者：
Salyer, Alex C. D.;David, Sunil A.
疫苗开发的一个重要组成部分是鉴定安全有效的佐剂。我们试图使用下一代RNA测序来鉴定先天免疫刺激分子的转录组特征，目的是能够利用这些特征来鉴定具有佐剂活性的新型免疫刺激化合物。CC家族的趋化因子，特别是CC趋化因子1、2、3、4、7、8、17、18、20和23，被大多数Toll样受体（TLR）和核苷酸结合结构域和富含亮氨酸的重复序列的受体（NLR）刺激广泛上调。细胞外受体如TLR 2、TLR 4和TLR 5诱导CXC趋化因子包括CXCL 5、CXCL 6和CXCL 8的转录，而细胞内受体如TLR 7和TLR 8上调CXC趋化因子11和12。TLR 1/2和TLR 2/6激动剂均诱导人外周血单核细胞产生强趋化因子。人骨骼肌细胞和成纤维细胞仅对TLR 2/6激动剂而非TLR 1/2激动剂产生趋化因子应答，这与成纤维细胞中TLR 2和TLR 6而非TLR 1的强表达一致。TLR 2/6刺激的成纤维细胞表现出对人T细胞和自然杀伤细胞亚群的功能性趋化反应。非造血外膜细胞如成纤维细胞和肌细胞的活化可能起作用。
An important component of vaccine development is the identification of safe and effective adjuvants. We sought to identify transcriptomal signatures of innate immune stimulating molecules using nextgeneration RNA sequencing with the goal of being able to utilize such signatures in identifying novel immunostimulatory compounds with adjuvant activity. The CC family of chemokines, particularly CC chemokines 1, 2, 3, 4, 7, 8, 17, 18, 20, and 23, were broadly upregulated by most Toll-like receptor (TLR) and nucleotide-binding domain and leucine-rich repeat-containing receptors (NLR) stimuli. Extracellular receptors such as TLR2, TLR4 and TLR5 induced the transcription of CXC chemokines including CXCL5, CXCL6 and CXCL8, whereas intracellular receptors such as TLR7 and TLR8 upregulated CXC chemokines 11 and 12. Both TLR1/2 and TLR2/6 agonists induced strong chemokine production in human peripheral blood mononuclear cells. Human skeletal muscle cells and fibroblasts respond with chemokine production only to TLR2/6 agonists, but not TLR1/2 agonists, consistent with strong expression of TLR2 and TLR6, but not of TLR1, in fibroblasts. TLR2/6 stimulated fibroblasts demonstrated functional chemotactic responses to human T cell and natural killer cells subsets. The activation of non-hematopoietic, adventitial cells such as fibroblasts and myocytes may contribute.