Mycobacterium tuberculosis YrbE3A Promotes Host Innate Immune Response by Targeting NF-kappa B/JNK Signaling

文献类型： 外文期刊

第一作者： Wang, Jieru

作者： Wang, Jieru;Zhu, Xiaojie;Peng, Yongchong;Zhu, Tingting;Liu, Han;Zhu, Yifan;Xiong, Xuekai;Chen, Xi;Hu, Changmin;Chen, Huanchun;Chen, Yingyu;Guo, Aizhen;Wang, Jieru;Wang, Jieru;Zhu, Xiaojie;Peng, Yongchong;Zhu, Tingting;Liu, Han;Zhu, Yifan;Xiong, Xuekai;Chen, Xi;Hu, Changmin;Chen, Huanchun;Chen, Yingyu;Guo, Aizhen;Zhu, Xiaojie;Chen, Yingyu;Guo, Aizhen;Chen, Yingyu;Guo, Aizhen

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关键词： Mycobacterium tuberculosis; YrbE3A; macrophages; proinflammatory cytokines; signaling pathways

期刊名称：MICROORGANISMS （ 影响因子：4.128； ）

ISSN：

年卷期： 2020 年 8 卷 4 期

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收录情况： SCI

摘要： Mycobacterium tuberculosis is considered a successful pathogen with multiple strategies to undermine host immunity. The YrbE3A is encoded by Rv1964 within the RD15 region present in the genome of Mtb, but missing in M. bovis, M. bovis BCG (Pasteur) strain, and M. smegmatis (Ms). However, little is known about its function. In this study, the YrbE3A gene was cloned into pMV261 and expressed in Ms and BCG, while the strains with the vector served as the controls. The YrbE3A was expressed on the mycobacterial membrane, and the purified protein could stimulate RAW264.7 cells to produce IL-6. Furthermore, the effect of the recombinant strains on cytokine secretion by RAW264.7 was confirmed, which varied with the host strains. Ms_YrbE3A increased significantly higher levels of TNF-alpha and IL-6 than did Ms_vec, while BCG_YrbE3A enhanced higher TNF-alpha than BCG_vec. The pathways associated with NF-kappa B p65 and MAPK p38/JNK, other than Erk1/2, regulated this process. In addition, mice were infected with Ms_YrbE3A and Ms-vec and were kinetically examined. Compared to Ms-vec, Ms_YrbE3A induced more serious inflammatory damage, higher levels of TNF-alpha and IL-6, higher numbers of lymphocytes, neutrophils, and monocytes in a time-dependent way, but lower lung bacterial load in lung. These findings may contribute to a better understanding of Mtb pathogenesis.

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