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首页> 外文期刊>Infection and immunity >Lack of Immune Responses to Mycobacterium tuberculosis DosR Regulon Proteins following Mycobacterium bovis BCG Vaccination
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Lack of Immune Responses to Mycobacterium tuberculosis DosR Regulon Proteins following Mycobacterium bovis BCG Vaccination

机译：牛分枝杆菌卡介苗接种后对结核分枝杆菌DosR Regulon蛋白缺乏免疫应答

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Mycobacterium bovis BCG is widely used as a vaccine against tuberculosis (TB), despite its variable protective efficacy. Relatively little is known about the immune response profiles following BCG vaccination in relation to protection against TB. Here we tested whether BCG vaccination results in immune responses to DosR (Rv3133c) regulon-encoded proteins. These so-called TB latency antigens are targeted by the immune system during persistent Mycobacterium tuberculosis infection and have been associated with immunity against latent M. tuberculosis infection. In silico analysis of the DosR regulon in BCG and M. tuberculosis showed at least 97% amino acid sequence homology, with 41 out of 48 genes being identical. Transcriptional profiling of 14 different BCG strains, under hypoxia and nitric oxide exposure in vitro, revealed a functional DosR regulon similar to that observed in M. tuberculosis. Next, we assessed human immune responses to a series of immunodominant TB latency antigens and found that BCG vaccination fails to induce significant responses to latency antigens. Similar results were obtained with BCG-vaccinated BALB/c mice. In contrast, responses to latency antigens were observed in individuals with suspected exposure to TB (as indicated by positive gamma interferon responses to TB-specific antigens ESAT-6 and CFP-10) and in mice vaccinated with plasmid DNA encoding selected latency antigens. Since immune responses to TB latency antigens have been associated with control of latent M. tuberculosis infection, our findings support the development of vaccination strategies incorporating DosR regulon antigens to complement and improve the current BCG vaccine.
机译：牛分枝杆菌 BCG尽管具有不同的保护功效，但仍被广泛用作抗结核疫苗。相对于针对结核病的保护，对卡介苗接种后的免疫应答特征知之甚少。在这里，我们测试了BCG疫苗接种是否导致对DosR（Rv3133c）调节子编码蛋白的免疫反应。这些所谓的TB潜伏期抗原在持续性结核分枝杆菌感染期间被免疫系统靶向，并与针对潜伏性 M的免疫力有关。结核感染。对BCG和 M中的DosR regulon进行计算机分析。结核病显示至少97％的氨基酸序列同源性，在48个基因中有41个相同。在体外低氧和一氧化氮暴露下，对14种不同BCG菌株的转录谱分析显示，功能性DosR调节子与 M中观察到的相似。结核病。接下来，我们评估了人类对一系列免疫显性结核病潜伏期抗原的免疫反应，发现卡介苗接种未能诱导对潜伏期抗原的显着反应。用接种了BCG的BALB / c小鼠获得了相似的结果。相反，在怀疑暴露于TB的个体中观察到对潜伏期抗原的反应（如对TB特异性抗原ESAT-6和CFP-10的伽马干扰素阳性反应所示），在接种了编码选定潜伏期抗原的质粒DNA的小鼠中也观察到了这种反应。由于对结核病潜伏期的免疫反应，抗原与控制潜在的 M有关。结核感染，我们的发现支持结合DosR regulon抗原的疫苗接种策略的发展，以补充和改进目前的BCG疫苗。

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