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首页> 外文期刊>Infection and immunity >Mycobacterium tuberculosis Culture Filtrate Proteins plus CpG Oligodeoxynucleotides Confer Protection to Mycobacterium bovis BCG-Primed Mice by Inhibiting Interleukin-4 Secretion
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Mycobacterium tuberculosis Culture Filtrate Proteins plus CpG Oligodeoxynucleotides Confer Protection to Mycobacterium bovis BCG-Primed Mice by Inhibiting Interleukin-4 Secretion

机译：结核分枝杆菌培养滤液蛋白和CpG寡脱氧核苷酸通过抑制白介素4分泌对牛分枝杆菌BCG介导的小鼠提供保护

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Culture filtrate proteins (CFP) are potential targets for tuberculosis vaccine development. We previously showed that despite the high level of gamma interferon (IFN-γ) production elicited by homologous immunization with CFP plus CpG oligodeoxynucleotides (CFP/CpG), we did not observe protection when these mice were challenged with Mycobacterium tuberculosis. In order to use the IFN-γ-inducing ability of CFP antigens, in this study we evaluated a prime-boost heterologous immunization based on CFP/CpG to boost Mycobacterium bovis BCG vaccination in order to find an immunization schedule that could induce protection. Heterologous BCG-CFP/CpG immunization provided significant protection against experimental tuberculosis, and this protection was sustained during the late phase of infection and was even better than that conferred by a single BCG immunization. The protection was associated with high levels of antigen-specific IFN-γ and interleukin-17 (IL-17) and low IL-4 production. The deleterious role of IL-4 was confirmed when IL-4 knockout mice vaccinated with CFP/CpG showed consistent protection similar to that elicited by BCG-CFP/CpG heterologous immunization. These findings show that a single dose of CFP/CpG can represent a new strategy to boost the protection conferred by BCG vaccination. Moreover, different immunological parameters, such as IFN-γ and IL-17 and tightly regulated IL-4 secretion, seem to contribute to the efficacy of this tuberculosis vaccine.
机译：培养滤液蛋白（CFP）是结核病疫苗开发的潜在目标。先前我们已经证明，尽管通过CFP加CpG寡脱氧核苷酸（CFP / CpG）同源免疫引发了高水平的γ-干扰素（IFN-γ）产生，但是当这些小鼠受到结核分枝杆菌攻击时，我们并未观察到保护作用。 em>。为了利用CFP抗原的IFN-γ诱导能力，在本研究中，我们评估了基于CFP / CpG的初免-加强型异源免疫，以加强牛分枝杆菌BCG疫苗的免疫接种，以找到免疫方法。可能引起保护的时间表。异种BCG-CFP / CpG免疫为实验性结核病提供了显着的保护，这种保护在感染后期得以维持，甚至比单次BCG免疫所提供的保护还要好。这种保护作用与高水平的抗原特异性IFN-γ和白介素17（IL-17）和低的IL-4产生有关。当接种了CFP / CpG的IL-4敲除小鼠表现出与BCG-CFP / CpG异源免疫相似的保护作用时，证实了IL-4的有害作用。这些发现表明，单剂量的CFP / CpG可以代表一种新的策略来增强BCG疫苗接种所赋予的保护作用。此外，不同的免疫学参数，例如IFN-γ和IL-17和严格调节的IL-4分泌，似乎有助于这种结核病疫苗的功效。

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