Sirtuin inhibits M. tuberculosis -induced apoptosis in macrophage through glycogen synthase kinase-3β

Abstract

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.