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首页> 外文期刊>Cytokine >Critical role of TRIF and MyD88 in Mycobacterium tuberculosis Hsp70-mediated activation of dendritic cells
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Critical role of TRIF and MyD88 in Mycobacterium tuberculosis Hsp70-mediated activation of dendritic cells

机译：TRIF和MyD88在结核分枝杆菌Hsp70介导的树突状细胞激活中的关键作用

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摘要

As a potent immune regulator, heat shock protein 70 derived from Mycobacterium tuberculosis (Mtb Hsp70) has adjuvant effect and activates immune cells such as macrophages and dendritic cells (DCs). Although Toll-like receptors (TLRs) are known to involve in DCs activation by Mtb Hsp70, there is still a controversy and the underlying mechanism is not well understood. In this study, we examined whether TRIF and MyD88, the core adaptor molecules for TLRs signaling, regulate Mtb Hsp70-induced DCs activation. Although Mtb Hsp70 produced substantial level of cytokines (IL-6, IL-12p40, and TNF-alpha) in TRIF-deficient DCs in a dose-dependent manner, each level was significantly lower than that in WT cells. The cytokines production was almost abolished in MyD88-deficient DCs. Consistent with cytokine results, Mtb Hsp70-induced activation of NF-kappa B and MAPKs was also impaired in both TRIF- and MyD88-deficient DCs, as compared with WT cells. Inhibitor assay revealed that NF-kappa B, ERK, and JNK, but not p38, regulate Mtb Hsp70-induced production of cytokines. In addition, the up-regulation of costimulatory molecules and MHC class II was mostly TRIF-dependent in DCs in response Mtb Hsp70, whereas MyD88 was only partially involved. Finally, mixed leukocytes reaction (MLR) assay revealed that both TRIF and MyD88 are critical for DCs ability promoted by Mtb Hsp70 to differentiate naive T cells into effector T cells of producing IFN-gamma. Our findings suggest that both TRIF and MyD88 are essential for the activation and maturation of DCs in response to Mtb Hsp70. (C) 2014 Elsevier Ltd. All rights reserved.
机译：作为有效的免疫调节剂，源自结核分枝杆菌的热激蛋白70（Mtb Hsp70）具有佐剂作用，并激活免疫细胞，例如巨噬细胞和树突状细胞（DC）。尽管已知Toll样受体（TLR）参与Mtb Hsp70激活DC，但仍存在争议，其潜在机制尚不明确。在这项研究中，我们检查了TRIF和MyD88（TLR信号转导的核心衔接子分子）是否调节Mtb Hsp70诱导的DC激活。尽管Mtb Hsp70在TRIF缺陷型DC中产生了大量的细胞因子（IL-6，IL-12p40和TNF-α），并且呈剂量依赖性，但每个水平均显着低于WT细胞。在缺乏MyD88的DC中，细胞因子的产生几乎被消除了。与细胞因子结果一致，与WT细胞相比，在TRIF和MyD88缺失的DC中，Mtb Hsp70诱导的NF-κB和MAPKs的活化也受到损害。抑制剂分析显示，NF-κB，ERK和JNK而非p38调节Mtb Hsp70诱导的细胞因子产生。另外，应答Mtb Hsp70的DC中，共刺激分子和II类MHC的上调主要是TRIF依赖性的，而MyD88仅部分参与。最后，混合白细胞反应（MLR）分析表明，TRIF和MyD88都对由Mtb Hsp70促进的DCs的能力至关重要，该能力使Mtb Hsp70将幼稚T细胞分化为产生IFN-γ的效应T细胞。我们的研究结果表明，TRIF和MyD88都对DC对Mtb Hsp70的激活和成熟至关重要。 （C）2014 Elsevier Ltd.保留所有权利。

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