Mycobacterium tuberculosis heat-shock protein 70 impairs maturation of dendritic cells from bone marrow precursors, induces interleukin-10 production and inhibits T-cell proliferation in vitro
Mycobacterium tuberculosis heat-shock protein 70 impairs maturation of dendritic cells from bone marrow precursors, induces interleukin-10 production and inhibits T-cell proliferation in vitro
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DOI：
10.1111/j.1365-2567.2007.02564.x
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发表时间：
2007-08-01
期刊：
影响因子：
6.4
通讯作者：
Bonorino, Cristina
中科院分区：
文献类型：
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作者：
Motta, Adriana;Schmitz, Carla;Bonorino, Cristina
在不同的炎症性疾病模型中，热休克蛋白(HSP)及其衍生的多肽已被证明具有抗炎作用。虽然一些研究表明热休克蛋白可以直接与抗原提呈细胞相互作用，但也有研究报道细菌热休克蛋白可以诱导具有调节表型的特定T细胞。然而，HSP70免疫调节作用的有效表征历来受到脂多糖(LPS)污染的干扰。在这项研究中，我们比较了无内毒素的结核分枝杆菌HSP70(TBhsp70)及其可能的污染物对树突状细胞(DC)的影响。在此，我们证明了无内毒素的TBhsp70在体外抑制小鼠DC的成熟，而被内毒素污染的TBhsp70诱导DC成熟。模拟重组制剂不起作用。与脂多糖不同，TBhsp70不能诱导DC产生肿瘤坏死因子-α，但能诱导IL-10的产生。在体内，只有脂多糖污染的TBhsp70才能诱导脾成熟DC CD86表达上调。最后，TBhsp70抑制植物血凝素诱导的T细胞增殖。我们的结果支持这样的假设，即TBhsp70不具有炎症潜能，而是具有免疫抑制特性。
In different inflammatory disease models, heat-shock proteins (hsp) and hsp-derived peptides have been demonstrated to possess anti-inflammatory properties. While some studies have shown that hsp can directly interact with antigen-presenting cells, others report that bacterial hsp can induce specific T cells with regulatory phenotypes. Effective characterization of the immunomodulatory effects of hsp 70, however, has historically been confounded by lipopolysaccharide (LPS) contamination. In this study, we compared the effects of LPS-free Mycobacterial tuberculosis hsp 70 (TBhsp70) and its possible contaminants on dendritic cells (DC). We demonstrate herein that LPS-free TBhsp70 inhibits murine DC maturation in vitro, while LPS-contaminated TBhsp70 induces DC maturation. Mock recombinant preparations have no effect. In contrast to LPS, TBhsp70 does not induce tumour necrosis factor-alpha production by DC, but interleukin-10. In vivo, only LPS-contaminated TBhsp70 induces up-regulation of CD86 in splenic mature DC. Finally, TBhsp70 inhibited phytohaemagglutinin-induced T-cell proliferation. Our results support the hypothesis that TBhsp70 does not have inflammatory potential, but rather has immunosuppressive properties.