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结核分枝杆菌Rv3435c基因调节炎性细胞因子,并参与小鼠的肺损伤和分枝杆菌存活。

Mycobacterium tuberculosis Rv3435c gene regulates inflammatory cytokines and is involved in lung injury and mycobacterial survival in mice.

作者信息

Liu Xin-Yue, Li Dan-Ni, Shi Kun, Li Jian-Ming, Zong Ying, Diao Nai-Chao, Zeng Fan-Li, Du Rui

机构信息

College of Animal Science and Technology, Jilin Agricultural University, Changchun, China.

College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun, China; Jilin Province Sika Deer Efficient Breeding and Product Development Technology Engineering Research Center, Changchun, China.

出版信息

Microb Pathog. 2025 Feb;199:107247. doi: 10.1016/j.micpath.2024.107247. Epub 2025 Jan 3.

Abstract

Mycobacterium tuberculosis enters the body through the respiratory tract, produces and releases virulence proteins through a variety of mechanisms, regulates the host immune mechanism through a variety of ways, and then survives in the body for a long time. These depend on virulence genes encoded by Mycobacterium tuberculosis. Previous studies found that the Rv3435c gene of Mycobacterium tuberculosis is highly conserved in pathogenic mycobacterium, but not conserved in non-pathogenic mycobacterium, which may be a potential virulence gene, and inhibit the secretion of inflammatory factors in RAW264.7 cells and inhibit cell apoptosis. Based on previous studies, the function of Rv3435c gene in mice was studied by infecting mice with recombinant strains. In vivo infection experiments showed that overexpression of Rv3435c significantly promoted the survival of Ms in the lung. Ms-pMV361-Rv3435c specifically inhibits the secretion of inflammatory cytokines, including TNF-α, IL-6, IL-1β, IL-12, and IFN-γ. Rv3435c can inhibit lung cell apoptosis and cause pathological damage to lung. Therefore, Rv3435c enhances the survival of mycobacterium in mice and promotes the pathogenicity and spread of Mycobacterium tuberculosis by inhibiting the production of cytokines.

摘要

结核分枝杆菌通过呼吸道进入人体,通过多种机制产生并释放毒力蛋白,通过多种方式调节宿主免疫机制,进而在体内长期存活。这些都依赖于结核分枝杆菌编码的毒力基因。以往研究发现,结核分枝杆菌的Rv3435c基因在致病性分枝杆菌中高度保守,但在非致病性分枝杆菌中不保守,它可能是一个潜在的毒力基因,能抑制RAW264.7细胞中炎性因子的分泌并抑制细胞凋亡。基于以往研究,通过用重组菌株感染小鼠来研究Rv3435c基因在小鼠体内的功能。体内感染实验表明,Rv3435c的过表达显著促进了结核分枝杆菌在肺部的存活。Ms-pMV361-Rv3435c特异性抑制炎性细胞因子的分泌,包括TNF-α、IL-6、IL-1β、IL-12和IFN-γ。Rv3435c可抑制肺细胞凋亡并对肺造成病理损伤。因此,Rv3435c通过抑制细胞因子的产生增强了分枝杆菌在小鼠体内的存活,并促进了结核分枝杆菌的致病性和传播。

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