Guangdong Provincial Key Laboratory of Medical Immunology and Molecular Diagnostics, School of Medical Technology, Guangdong Medical University, Dongguan, China.
Dongguan Key Laboratory of Molecular Immunology and Cell Therapy, Guangdong Medical University, Dongguan, China.
Front Cell Infect Microbiol. 2024 Oct 4;14:1455819. doi: 10.3389/fcimb.2024.1455819. eCollection 2024.
Tuberculosis(TB), an infectious disease caused by (Mtb) infections, remains the leading cause of mortality from a single infectious agent globally. The progression of tuberculosis disease is contingent upon the complex interplay between the host's immune system and the pathogen Mtb. Interleukin-26 (IL-26), the most recently identified cytokine belonging to the IL-10 family, exhibits both extracellular antimicrobial properties and pro-inflammatory functions. However, the precise role of IL-26 in the host immune defense against Mtb infections and intracellular killing remains largely unexplored. In this study, we observed significantly elevated IL-26 mRNA expression in peripheral blood mononuclear cells of active-TB patients compared to healthy individuals. Conversely, circulating IL-26 levels in the plasma of adult TB patients were markedly lower than those of healthy cohorts. We purified recombinant IL-26 from an . coli expression system using the Ni-NTA resin. Upon stimulations with the recombinant IL-26, human THP1 cells exhibited rapid morphological changes characterized by increased irregular spindle shape and formation of granular structures. Treating THP1 cells with IL-26 can also lead to heightened expressions of , , and but not and in these cells, indicating an M1 macrophage differentiation phenotype. Furthermore, our investigations revealed a dose-dependent escalation of reactive oxygen species production, decreased mitochondrial membrane potential, and enhanced autophagy flux activity in THP1 macrophages following IL-26 treatment. Moreover, our results demonstrated that IL-26 contributed to the elimination of intracellular Mycobacterium tuberculosis via orchestrated ROS production. In conclusion, our findings elucidated the role of IL-26 in the development of tuberculosis and its contributions to intracellular bacilli killing by macrophages through the induction of M1-polarization and ROS production. These insights may have significant implications for understanding the pathogenesis of tuberculosis and developing novel therapeutic strategies.
结核病（TB）是一种由（Mtb）感染引起的传染病，仍然是全球由单一感染源导致死亡的主要原因。结核病的发展取决于宿主免疫系统和病原体 Mtb 之间的复杂相互作用。白细胞介素-26（IL-26）是最近发现的属于白细胞介素-10 家族的细胞因子，具有细胞外抗菌特性和促炎功能。然而，IL-26 在宿主免疫防御 Mtb 感染和细胞内杀伤中的确切作用在很大程度上仍未得到探索。在这项研究中，我们观察到活动性 TB 患者外周血单个核细胞中 IL-26 mRNA 表达明显升高，而健康个体则没有。相反，成人 TB 患者血浆中循环的 IL-26 水平明显低于健康对照组。我们使用 Ni-NTA 树脂从大肠杆菌表达系统中纯化了重组 IL-26。在重组 IL-26 的刺激下，人 THP1 细胞表现出快速的形态变化，特征为不规则的纺锤形增加和颗粒结构的形成。用 IL-26 处理 THP1 细胞也可以导致这些细胞中 、 、 和 的表达增加，但 和 没有增加，表明 M1 巨噬细胞分化表型。此外，我们的研究还揭示了 IL-26 处理后 THP1 巨噬细胞中活性氧物质产生、线粒体膜电位降低和自噬通量活性增强呈剂量依赖性增加。此外，我们的结果表明，IL-26 通过协调 ROS 产生有助于消除细胞内结核分枝杆菌。总之，我们的研究结果阐明了 IL-26 在结核病发展中的作用及其通过诱导 M1 极化和 ROS 产生促进巨噬细胞杀伤细胞内细菌的作用。这些发现可能对理解结核病的发病机制和开发新的治疗策略具有重要意义。
