Key Laboratory of Ministry of Education for Conservation and Utilization of Special Biological Resources in the Western, Ningxia University, Yinchuan, Ningxia, 750021, China; School of Life Sciences, Ningxia University, Yinchuan, Ningxia, 750021, China.
Key Laboratory of Ministry of Education for Conservation and Utilization of Special Biological Resources in the Western, Ningxia University, Yinchuan, Ningxia, 750021, China; School of Life Sciences, Ningxia University, Yinchuan, Ningxia, 750021, China; Key Laboratory of Hui Ethnic Medicine Modernization Ministry of Education, Ningxia Medical University, Yinchuan, 750004, China.
Microb Pathog. 2022 Dec;173(Pt A):105826. doi: 10.1016/j.micpath.2022.105826. Epub 2022 Oct 13.
Autophagy functions as a critical process that can suppress the proliferation of Mycobacterium tuberculosis (Mtb) within infected host cells. Wnt5a is a secreted protein that plays a range of physiological functions, activating several signaling pathways and thereby controlling cellular responses to particular stimuli. The importance of Wnt5a as a regulator of protection against Mtb infection, however, has yet to be fully characterized. Here, changes in murine pulmonary epithelial-like TC-1 cell morphology, autophagy, the Wnt/Ca signaling pathway, and the mTOR autophagy pathway were analyzed following infection with the Mtb model pathogen Bacille Calmette-Guerin (BCG) in order to understand the regulatory role of Wnt5a in this context. These experiments revealed that Wnt5a was upregulated and autophagy was enhanced in TC-1 cells infected with BCG, and Wnt5a overexpression was found to drive BCG-induced autophagy in these cells upon infection, whereas the inhibition or knockdown of Wnt5a yielded the opposite effect. At the mechanistic level, Wnt5a was found to mediate non-canonical Wnt/Ca signaling and thereby inhibit mTOR-dependent pathway activation, promoting autophagic induction within BCG-infected TC-1 cells. These data offer new insight regarding how Wnt5a influences Mtb-induced autophagy within pulmonary epithelial cells, providing a foundation for further research exploring the immunological control of this infection through the modulation of autophagy.
自噬作为一种重要的过程，可以抑制感染宿主细胞内结核分枝杆菌（Mtb）的增殖。Wnt5a 是一种分泌蛋白，具有多种生理功能，激活多种信号通路，从而控制细胞对特定刺激的反应。然而，Wnt5a 作为抵抗 Mtb 感染的保护因子的重要性尚未得到充分表征。在这里，为了了解 Wnt5a 在这种情况下的调节作用，分析了感染结核分枝杆菌模型病原体卡介苗（BCG）后，鼠肺上皮样 TC-1 细胞形态、自噬、Wnt/Ca 信号通路和 mTOR 自噬通路的变化。这些实验表明，BCG 感染 TC-1 细胞后 Wnt5a 上调，自噬增强，Wnt5a 过表达可驱动感染后 BCG 诱导的自噬，而 Wnt5a 的抑制或敲低则产生相反的效果。在机制水平上，发现 Wnt5a 介导非经典 Wnt/Ca 信号通路，从而抑制 mTOR 依赖性通路的激活，促进 BCG 感染的 TC-1 细胞中的自噬诱导。这些数据提供了关于 Wnt5a 如何影响肺上皮细胞中 Mtb 诱导的自噬的新见解，为通过调节自噬进一步研究这种感染的免疫控制提供了基础。
