Co-stimulation with TLR3 and TLR21 ligands synergistically up-regulates Th1-cytokine IFN-γ and regulatory cytokine IL-10 expression in chicken monocytes
Co-stimulation with TLR3 and TLR21 ligands synergistically up-regulates Th1-cytokine IFN-γ and regulatory cytokine IL-10 expression in chicken monocytes
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DOI：
10.1016/j.dci.2011.11.006
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发表时间：
2012-04-01
影响因子：
2.9
通讯作者：
Kogut, Michael H.
中科院分区：
文献类型：
--
作者：
He, Haiqi;Genovese, Kenneth J.;Kogut, Michael H.
Toll 样受体 (TLR) 是先天免疫系统对各种保守的病原体相关分子基序的模式识别受体。鸡 TLFt3 和 TLR21（相当于哺乳动物 TLR9 的禽类）分别识别 Poly I:C（双链 RNA）和 CpG-ODN（含有寡脱氧核苷酸的 CpG 基序）。据报道，TLR3 和 TLR21 激动剂 Poly I:C 和 CpG-ODN 之间的相互作用可协同促进鸡单核细胞中促炎细胞因子和趋化因子的表达以及一氧化氮的产生。然而，poly I:C 和 CpG-ODN 对干扰素 (IFN) 和 Th1/Th2 细胞因子表达的相互作用仍不清楚。本研究的目的是探讨poly I:C和CpG-ODN之间的相互作用对鸡单核细胞中IFN-α和IFN-β、Th1细胞因子IFN-γ和IL-12、Th2细胞因子IL-4和调节性IL-10 mRNA表达水平的影响。当单独使用任一激动剂刺激时，CpG-ODN 显着上调 INF-γ、IL-10 和 IL-12p40 的表达，但不上调 IFN-α 和 IFN-β；而 Poly I:C 诱导 INF-γ、IFN-α、IFN-β 和 IL-10 的表达；但不是 IL-12p40。然而，CpG-ODN 和 Poly I:C 的组合刺激进一步协同增加了 IFN-γ 和 IL-10 mRNA 的表达。我们的结果提供了强有力的证据，支持 TLR3 和 TLR21 在禽类针对病毒和细菌感染的先天免疫中发挥关键作用； TLR3 和 TLR21 通路之间的协同相互作用在鸡单核细胞中产生更强的 Th1 偏向免疫反应。我们的结果还表明，poly I:C 和 CpG-ODN 可能一起用作家禽疫苗开发的更有效佐剂。由爱思唯尔有限公司出版
Toll-like receptors (TLRs) are pattern recognition receptors of the innate immune system for various conserved pathogen-associated molecular motifs. Chicken TLFt3 and TLR21 (avian equivalent to mammalian TLR9) recognize poly I:C (double-stranded RNA) and CpG-ODN (a CpG-motif containing oligodeoxydinu-cleotide), respectively. Interaction between TLR3 and TLR21 agonists poly I:C and CpG-ODN has been reported to synergize in expression of proinflammatory cytokines and chemokines and the production of nitric oxide in chicken monocytes. However, the interaction between poly I:C and CpG-ODN on the expression of interferons (IFNs) and Th1/Th2 cytokines remains unknown. The objective of the present study was to investigate the effect of the interaction between poly I:C and CpG-ODN on the mRNA expression levels of IFN-alpha and IFN-beta, Th1 cytokines IFN-gamma and IL-12, Th2 cytokine IL-4, and regulatory IL-10 in chicken monocytes. When stimulated with either agonist alone, CpG-ODN significantly up-regulated the expression of INF-gamma, IL-10, and IL-12p40, but not IFN-alpha and IFN-beta; whereas poly I:C induced the expression of INF-gamma, IFN-alpha, IFN-beta, and IL-10; but not IL-12p40. However, stimulation with a combinatory CpG-ODN and poly I:C further synergistically increased the expression of IFN-gamma and IL-10 mRNA. Our results provide strong evidence supporting the critical role of TLR3 and TLR21 in avian innate immunity against both viral and bacterial infections; and the synergistic interaction between the TLR3 and TLR21 pathways produces a stronger Th1-biased immune response in chicken monocytes. Our result also suggest a potential use of poly I:C and CpG-ODN together as a more efficient adjuvant for poultry vaccine development. Published by Elsevier Ltd.