Department of Microbiology and Immunology, School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou, China.
Key Laboratory of Laboratory Medicine, Ministry of Education of China, Wenzhou, China.
Front Cell Infect Microbiol. 2021 Jan 27;10:596609. doi: 10.3389/fcimb.2020.596609. eCollection 2020.
() is an estuarine bacterium that is capable of causing rapidly fatal infection in humans. Proper polarization and bactericidal activity of macrophages play essential roles in defending against invading pathogens. How macrophages limit infection remains not well understood. Here we report that tuberous sclerosis complex 1 (TSC1) is crucial for the regulation of -induced macrophage polarization, bacterial clearance, and cell death. Mice with myeloid-specific deletion of TSC1 exhibit a significant reduction of survival time after infection. infection induces both M1 and M2 polarization. However, TSC1 deficient macrophages show enhanced M1 response to infection. Interestedly, the absence of TSC1 in myeloid cells results in impaired bacterial clearance both and after infection. Inhibition of the mammalian target of rapamycin (mTOR) activity significantly reverses -induced hypersensitive M1 response and resistant bactericidal activity both in wild-type and TSC1-deficient macrophages. Moreover, infection causes cell death of macrophages, possibly contributes to defective of bacterial clearance, which also exhibits in a mTORC1-dependent manner. These findings highlight an essential role for the TSC1-mTOR signaling in the regulation of innate immunity against infection.
() 是一种河口细菌，能够在人类中引起迅速致命的感染。适当的极化和巨噬细胞的杀菌活性在抵御入侵病原体方面起着至关重要的作用。巨噬细胞如何限制感染仍然不太清楚。在这里，我们报告结节性硬化复合物 1 (TSC1) 对于调节诱导的巨噬细胞极化、细菌清除和细胞死亡至关重要。髓系特异性缺失 TSC1 的小鼠在感染后存活时间明显缩短。感染诱导 M1 和 M2 极化。然而，TSC1 缺陷型巨噬细胞对感染表现出增强的 M1 反应。有趣的是，髓系细胞中 TSC1 的缺失导致感染后细菌清除能力受损，无论是在感染后还是感染后。哺乳动物雷帕霉素靶蛋白 (mTOR) 活性的抑制显著逆转了野生型和 TSC1 缺陷型巨噬细胞中诱导的超敏 M1 反应和耐药杀菌活性。此外，感染导致巨噬细胞死亡，可能导致细菌清除缺陷，这也以 mTORC1 依赖性方式表现出来。这些发现强调了 TSC1-mTOR 信号在调节针对感染的先天免疫中的重要作用。
