Perspective Chapter: Interferon-Gamma in Natural Defence and Prevention of Leprosy

Mycobacterium leprae causes leprosy. M. leprae enters the body through the upper respiratory tract where it interacts with host’s cells. Interferon (IFN) is a class of cytokines in human body that are released in case of viral and intracellular pathogen infection and they activate the immune cells to eradicate those pathogens. IFN-γ (Type-II IFN) confers immunity against bacterial, viral, and protozoan diseases. Loss of function mutations in IFN-γ results in poor immunity towards mildly virulent mycobacterium. Upon M. leprae invasion, monocytes enter the site of infection and differentiates into macrophages. IFN-γ induces endothelial cells (EC) of the pathogenic micro-environment to cause monocyte differentiation into pro-inflammatory M1 macrophages for immediate antimicrobial activity. This differentiation is ceased in the absence of endothelial cells. M1 macrophages are clinically more active than anti-inflammatory M2 macrophages induced by resting EC. The former produced higher amounts of pro-inflammatory cytokines in response to the TLR2/1 ligand of M. leprae. The former also showed elevation of vitamin D-associated antimicrobial pathway genes, which are required to counter M. leprae. In addition, the former accumulates less oxidised LDL to prevent growth of M. leprae. Thus, advancement of IFN-γ research would help in the design of next-generation anti- leprosy therapeutics.