Abstract
Previous studies demonstrated that live Mycobacterium leprae (M. leprae) infection promoted macrophage differentiation toward the M2 type, with elevated interleukin (IL)-10 production. The underlying mechanism is not entirely clear. In this study, we treated macrophages with primary M. leprae strains isolated from both lepromatous leprosy (L-lep) and tuberculoid leprosy (T-lep) patients. We found that infection by live M. leprae, regardless of the primary strain, resulted in M2 skewing in the infected macrophage. This skewing was associated with downregulated IRGM expression, a core organizer protein in the autophagy assembly and reduced autophagosome formation, and with lower annexin V staining and lower caspase 3 and caspase 9 activity. Moreover, live M. leprae-infected macrophages prevented efficient phagocytosis by uninfected bystander macrophages. As a result, the phagocytes secreted less pro-inflammatory cytokines, and preferentially primed anti-inflammatory T cell responses. Together, these results suggested that live M. leprae could employ a strain-independent mechanism to suppress inflammation, possibly involving the inhibition of autophagy and apoptosis in the infected macrophages.