Leprosy is a chronic infectious disease caused by Mycobacterium leprae, an obligate intracellular pathogen with tropism for macrophages and Schwann cells, predominantly affecting the skin and peripheral nerves. Despite the effectiveness of multidrug therapy (MDT) recommended by the World Health Organization (WHO), limitations such as emerging drug resistance, adverse effects, long therapeutic duration, and persistence of neurological sequelae stimulate the search for new therapeutic approaches. This systematic review analyzed the role of the leprosy microenvironment. In vitro and in vivo studies, molecular analyses, and systematic reviews involving mechanisms were included. The study highlights the relevance of lysosomes and their dynamics of the cellular microenvironment in bacillary persistence and the immune response to leprosy. In this context, strategies integrating pathophysiology and immunomodulation emerge as promising perspectives for the development of new anti-leprosy agents.
