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结核分枝杆菌蛋白 Rv2652c 通过抑制宿主免疫反应增强细胞内生存能力。

Mycobacterium tuberculosis protein Rv2652c enhances intracellular survival by inhibiting host immune responses.

机构信息

Yichang Key Laboratory of Integrated Traditional Chinese and Western Medicine for the Prevention and Treatment of Immunological Diseases, The Second People's Hospital of China Three Gorges University, Yichang, China.

Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, China Three Gorges University, Yichang, China.

出版信息

Immun Inflamm Dis. 2024 Sep;12(9):e70012. doi: 10.1002/iid3.70012.

Abstract

BACKGROUNDS

Mycobacterium tuberculosis (Mtb), the pathogen responsible for tuberculosis, secretes a multitude of proteins that modulate the host's immune response to ensure its own persistence. The region of difference (RD) genes encoding proteins play key roles in TB immunity and pathogenesis. Nevertheless, the roles of the majority of RD-encoded proteins remain to be elucidated.

OBJECTS

To elucidate the role of Rv2652c located in RD13 in Mtb on bacterial growth, bacterial survival, and host immune response.

METHODS

We constructed the strain MS_Rv2652c which over-expresses Mtb RD-encoding protein Rv2652c in M. smegmatis (MS), and compared it with the wild strain in the bacterial growth, bacterial survival, virulence of Rv2652c, and determined the effect of MS_Rv2652c on host immune response in macrophages.

RESULTS

Rv2652c protein is located at cell wall of MS_Rv2652c strain and also an integral component of the Mtb H37Rv cell wall. Rv2652c can enhance the resistance of recombinant MS to various stressors. Moreover, Rv2652c inhibits host proinflammatory responses via modulation of the NF-κB pathway, thereby promoting Mtb survival in vitro and in vivo.

CONCLUSION

Our data suggest that cell wall protein Rv2652c plays an important role in creating a favorable environment for bacterial survival by modulating host signals and could be established as a potential TB drug target.

摘要

背景

结核分枝杆菌(Mtb)是导致结核病的病原体,它分泌大量的蛋白质,调节宿主的免疫反应,以确保自身的持续存在。差异区(RD)基因编码的蛋白质在结核病的免疫和发病机制中起着关键作用。然而,大多数 RD 编码蛋白的作用仍有待阐明。

目的

阐明位于 RD13 中的 Mtb Rv2652c 基因在 Mtb 中的作用,包括对细菌生长、细菌存活和宿主免疫反应的影响。

方法

我们构建了在耻垢分枝杆菌(MS)中过表达 Mtb RD 编码蛋白 Rv2652c 的菌株 MS_Rv2652c,并与野生株进行比较,观察其在细菌生长、细菌存活、Rv2652c 毒力以及 MS_Rv2652c 对巨噬细胞宿主免疫反应的影响。

结果

Rv2652c 蛋白位于 MS_Rv2652c 菌株的细胞壁上,也是 Mtb H37Rv 细胞壁的一个组成部分。Rv2652c 可以增强重组 MS 对各种应激源的抗性。此外,Rv2652c 通过调节 NF-κB 通路抑制宿主的促炎反应,从而促进 Mtb 在体外和体内的存活。

结论

我们的数据表明,细胞壁蛋白 Rv2652c 通过调节宿主信号,在为细菌生存创造有利环境方面发挥着重要作用,它可能成为一个潜在的结核病药物靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d66/11378267/87dd3cceb797/IID3-12-e70012-g002.jpg

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