IFN-γ induced antimicrobial response against M. leprae in human macrophages (117.12)

Abstract

Abstract The role of IFN-γ in inducing an antimicrobial response in macrophages was investigated in leprosy, a disease caused by intracellular bacterium M. leprae. Tuberculoid leprosy (T-lep) is characterized by few skin lesions with low bacterial numbers, whereas lepromatous leprosy (L-lep) is characterized by disseminated skin lesions and increased bacilli numbers. The host immune response in T-lep is characterized by Th1 cytokines and expression of the vitamin D dependent antimicrobial pathway, in contrast to L-lep, which is predominately Th2. We have linked expression of the Th1 cytokine IFN-γ and antimicrobial response in leprosy by induction of vitamin D dependent antimicrobial response genes CAMP and DEFB4. IFN-γ is present in T-lep patients, where the disease is self-limited, however, the role of IFN-γ in antimicrobial activity is unclear. IFN-γ mediates antimicrobial activity against M. tuberculosis, a related pathogen, in the presence of vitamin D sufficient serum, but not in the presence of vitamin D deficient serum. Our preliminary data shows that M. leprae infected macrophages pretreated with IFN-γ prior to infection in combination with post-infection IFN-γ treatment in vitamin D sufficient serum reduced bacterial viability by approximately 80% compared to media control. Our studies suggest that IFN-γ can trigger a vitamin D dependent antimicrobial response in human macrophages as well as antimicrobial activity against M. leprae.