CD14+ cells are required for IL-12 response in bovine blood mononuclear cells activated with Toll-like receptor (TLR) 7 and TLR8 ligands
CD14+ cells are required for IL-12 response in bovine blood mononuclear cells activated with Toll-like receptor (TLR) 7 and TLR8 ligands
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DOI：
10.1016/j.vetimm.2008.08.001
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发表时间：
2008-12-15
影响因子：
1.8
通讯作者：
Mutwiri, George K.
中科院分区：
文献类型：
--
作者：
Buza, Joram;Benjamin, Ponn;Mutwiri, George K.
单链重要RNA （ssRNA）最近被鉴定为TLR7和TLR8的天然配体。来自病毒的ssRNA序列及其合成类似物刺激人类和小鼠免疫细胞的先天免疫反应，但其免疫刺激活性尚未在反刍动物中进行研究。在本研究中，我们测试了合成RNA寡核糖核苷酸（ORN）是否能激活牛的免疫细胞。orn诱导牛外周血单核细胞（PBMCs）产生IL-12、ifn - γ和tnf - α的体外培养未观察到ifn - α的显著诱导。从PBMC中去除CD14（+）细胞可以消除IL-12应答，从而消除ifn - γ应答，这表明CD14（+）细胞是ORN对PBMC免疫激活所必需的。与这些发现一致，在CD14（+）部分中，ORN的假定受体（TLR7和TLR8）的表达水平高于CD14(-) PBMC部分。在ORN刺激前用巴菲霉素（一种吞噬体酸化抑制剂）预处理PBMC可消除细胞因子反应，证实介导ORN诱导反应的受体是细胞内的。这些结果首次证明了TLR7/8激动剂ORN's在牛身上具有很强的免疫刺激作用，并表明TLR7/8配体在家畜中激活先天和适应性免疫反应的潜力值得进一步研究。(C) 2008 Elsevier B.V.版权所有
Single-stranded vital RNA (ssRNA) was recently identified as the natural ligand for TLR7 and TLR8. ssRNA sequences from viruses, as well as their synthetic analogues stimulate innate immune responses in immune cells from humans and mice, but their immunostimulatory activity has not been investigated in ruminants. In the present investigations, we tested whether synthetic RNA oligoribonucleotides (ORN) can activate immune cells from cattle. In vitro incubation of bovine peripheral blood mononuclear cells (PBMCs) with ORN-induced production of IL-12, IFN-gamma and TNF-alpha. No significant induction of IFN-alpha was observed. Depletion of CD14(+) cells from PBMC abrogated the IL-12 response and consequently the IFN-gamma response, suggesting that CD14(+) cells are required for PBMC immune activation with ORN. Consistent with these findings, the Putative receptors for ORN (TLR7 and TLR8) were expressed at higher levels in the CD14(+) fraction than the CD14(-) PBMC fraction. Pre-treatment of PBMC with bafilomycin (an inhibitor of phagosomal acidification) prior to Stimulation with ORN abolished the cytokine responses, confirming that the receptor(s) which mediate the ORN-induced responses are intracellular. These results demonstrate for the first time that the TLR7/8 agonist ORN's have strong immune stimulatory effects in cattle, and suggest that further investigation on the potential of TLR7/8 ligands to activate innate and adaptive immune responses in domestic animals are warranted. (C) 2008 Elsevier B.V. All rights reserved.