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结核分枝杆菌 DosR 蛋白在上调结核患者和健康接触者效应 T 细胞的同时下调 T 调节细胞。

DosR proteins of Mycobacterium tuberculosis upregulate effector T cells and down regulate T regulatory cells in TB patients and their healthy contacts.

机构信息

DS Kothari Centre for Research and Innovation in Science Education, Miranda House, and Department of Zoology, Miranda House, University of Delhi, Delhi, 110007, India.

Rajan Babu Institute of Pulmonary Medicine and Tuberculosis Hospital, GTB Nagar, Delhi, 110009, India.

出版信息

Microb Pathog. 2019 Jan;126:399-406. doi: 10.1016/j.micpath.2018.11.029. Epub 2018 Nov 23.

Abstract

It is well established that the current problem of tuberculosis (TB) can be combated by overcoming the drawbacks of the currently available BCG vaccine. This would involve incorporation of antigens that can control TB at all stages including the dormant phase which is generally ignored. Hence, DosR regulon proteins, which are expressed in latent infection, could prove to be very good vaccine candidates as they can possibly target the silent but most predominant form of TB infection. In the present study, the immune response to two DosR proteins Rv2627 and Rv2628 has been studied in PBMCs derived from normal individuals, TB patients and healthy contacts of TB patients. It was found that these antigens were capable of stimulating a strong IFN-γ+ T cell response along with accentuation of memory T cells and other protective cytokines such as IL-2 and IL-17. At the same time these proteins decreased the frequencies of immune-suppressor regulatory T cells in in vitro stimulation of PBMC from both patients and their contacts. Considering all these facts together, we suggest Rv2627 and Rv2628 to be one of the extremely promising candidates for incorporation into a post exposure subunit vaccine against TB.

摘要

现有资料充分表明,克服现有卡介苗(BCG)疫苗的缺陷,能够解决当前结核病(TB)的问题。这涉及到加入能够控制 TB 的抗原,包括通常被忽视的休眠期。因此,潜伏感染中表达的 DosR 调控蛋白可能成为非常好的疫苗候选物,因为它们可能针对沉默但最主要的 TB 感染形式。在本研究中,研究了源自正常人、TB 患者和 TB 患者健康接触者的 PBMC 对两种 DosR 蛋白 Rv2627 和 Rv2628 的免疫反应。结果发现,这些抗原能够刺激强烈的 IFN-γ+T 细胞反应,同时增强记忆 T 细胞和其他保护性细胞因子,如 IL-2 和 IL-17。同时,这些蛋白降低了 PBMC 在体外刺激中免疫抑制调节性 T 细胞的频率,无论是来自患者还是他们的接触者。综合所有这些事实,我们认为 Rv2627 和 Rv2628 是纳入针对 TB 的暴露后亚单位疫苗的极具前途的候选物之一。

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