Apoptotic and inflammatory pathways play important roles in Mycobacterium tuberculosis-infected macrophages. Sirt1 is a member of the deacetylase family that is known to promote apoptosis resistance in mammalian cells and was recently reported to regulate mycobacterial immunopathogenesis via inflammatory responses. However, the apoptotic role of Sirt1 in the process of M. tuberculosis infection remains unclear. With the help of mouse peritoneal macrophage samples, we have shown that resveratrol, a Sirt1 activator, inhibited M. tuberculosis-induced apoptosis in peritoneal macrophages. Further, we found that Sirt1 activation prompted M. tuberculosis induced GSK3β phosphorylation. Further investigation into the possible mechanisms of action showed that Sirt1 directly interacted with GSK3β and enhanced GSK3β phosphorylation by promoting its deacetylation. Sirt1 activation inhibited M. tuberculosis growth. Thus, it seemed that Sirt1 acted as a novel regulator of apoptosis signaling in M. tuberculosis infection via its direct effects on GSK3β. Sirt1 may therefore be a new candidate for the prevention and treatment of tuberculosis.

凋亡和炎性途径在结核分枝杆菌感染的巨噬细胞中起重要作用。Sirt1是脱乙酰基酶家族的成员，已知该家族可促进哺乳动物细胞的凋亡抗性，最近有报道称它通过炎症反应调节分枝杆菌的免疫发病机制。然而，Sirt1在结核分枝杆菌感染过程中的凋亡作用仍不清楚。借助于小鼠腹膜巨噬细胞样品，我们已经表明，白藜芦醇，Sirt1激活剂，抑制结核分枝杆菌诱导的腹膜巨噬细胞凋亡。此外，我们发现Sirt1激活提示结核分枝杆菌诱导的GSK3β磷酸化。对可能的作用机理的进一步研究表明，Sirt1与GSK3β直接相互作用，并通过促进其脱乙酰基作用增强了GSK3β的磷酸化。Sirt1激活抑制结核分枝杆菌的生长。因此，Sirt1似乎通过对GSK3β的直接作用而成为结核分枝杆菌感染中凋亡信号传导的新型调节剂。因此，Sirt1可能是预防和治疗结核病的新候选人。