Review of research progress on different modalities of Macrophage death in Mycobacterium leprae infection.

Leprosy, caused by Mycobacterium leprae (M. leprae), is a chronic infectious disease primarily affecting the skin and peripheral nerves. The interaction between M. leprae and macrophages, its primary host cell, plays a critical role in disease progression. This review explores the various forms of macrophage cell death induced by M. leprae infection, including apoptosis, autophagy, necroptosis, pyroptosis, ferroptosis and necrosis. The regulation and implications of these cell death pathways on the host immune response are discussed. Apoptosis and autophagy are highlighted as mechanisms that may limit M. leprae proliferation, while necroptosis and pyroptosis contribute to inflammation and immune response. Notably, recent studies have identified CYBB-mediated ferroptosis as essential for macrophages infected with M. leprae to polarize towards the M2 phenotype, facilitating immune evasion by the pathogen. This review underscores the complexity of macrophage cell death in leprosy, and summarize their corresponding molecular mechanisms and potential impact on the host immunity.