Executive Summary : | Post kala-azar Dermal Leishmaniasis (PKDL) is a neglected tropical disease causing skin lesions and hypopigmentation, which can lead to long-lasting adverse effects on quality of life. The causative species is the protozoan parasite, Leishmania donovani, which is confined to South Asia and East Africa. PKDL patients harbor parasites in skin lesions, which can sustain VL transmission. Skin hypopigmentation reflects a loss or defective melanocyte function, but the underlying mechanisms remain unclear. Inflammatory mediators, such as IL-18, IL-33, granulocyte-macrophage colony stimulating factor, IFN-?, IL-1, IL-4, IL-6, IL-17, and tumor necrosis factor, play a role in regulating melanogenesis. The inflammasome, a protein complex that activates caspase 1, is crucial in eliciting innate immune responses, as IL-1? has been suggested to contribute to various skin diseases. This study aims to characterize inflammasome activity in cells like keratinocytes in the epidermis and its role in melanocyte dysfunction in PKDL that may lead to hypopigmentation. Vitiligo, an autoimmune non-pathogen-mediated skin disease, is characterized by the destruction of skin melanocytes and patchy white spots. Deactivation of the NLRP3 inflammasome can impair CD8+ T cell recruitment and inhibit cytokine secretion in T-cells derived from vitiligo patients. In conclusion, PKDL is a neglected tropical disease that presents with skin hypopigmentation and other adverse effects. Understanding the role of inflammasome activity in PKDL and its potential role in hypopigmentation is essential for effective treatment. |