Research Projects

Post-Kala-azar Dermal Leishmaniasis (PKDL) presents a significant challenge to eradication of L. donovani in India, which appears as cutaneous lesions after apparent cure of Visceral Leishmaniasis (VL). PKDL serves as a reservoir for Leishmania parasites, contributing to ongoing disease transmission. PKDL appears in early macules, plaques and nodules. So far there are no different treatment strategies have evolved, except liposomal amphotericin B be the mainstay of treatment which are used for VL as well. However, the large number of untreated and increasing non responsive cases to existing treatment are likely to impede eradication of the disease. Which requires immediate attention in understanding of in-depth pathology, and drug escaping mechanisms of parasite in PKDL. Having no in vitro or in vivo models for PKDL, greatly limiting this possibility. In the light of disease eradication screening of parasite reservoirs (asymptomatic cases) and identifying new drug strategies are essential, which embarks the necessity to the develop an in vitro PKDL model. With increased drug resistance in leishmania it is yet to explore the underlined mechanisms for the origine of drug resistance and links to PKDL. Evidences of polymorphism in metabolism with increased Glycosome biogenesis to combat drug induced stress and death in parasite and horizontal gene/protein transfer by Extra cellular Vesicles (EVs) raise the concerns on their role in manifesting the host microenvironment in PKDL for the immune invasion and persistence under the skin. Early stage of PKDL know as macular stage is characterized by depigmentation with rare / less load parasite observed, after apparent cure of VL. It is still unclear that, what interactions make melanocytes to lose the pigmentation and how parasite is achieving the destruction of melanocytes in their absence also is an unexplored question. In the present study we propose to optimize conditions for growing triple co-cultures of Melanocyte/Keratinocyte - parasite infected macrophage co-cultures and explore the molecular interactions which regulate the de pigmentation process. We also anticipate, to explore the role of extra cellular vesicles from wild vs drug-resistant L. donovani (not explored for Indian PKDL) and possibilities for establishing an in-vitro model of Melanocyte/Keratinocyte - parasite infected macrophage co-cultures-based model to explore clues on molecular interactions, which paves platform for early diagnosis and to screen novel drug molecules in future. We believe, the outcome of the project will enable us to understand conditions required to grow parasite infected macrophage along with other cells, the role of drug-resistant parasite secretions and their relevance in macular stage development of disease as a forego for setting up a complete in-vitro 3-D skin model of PKDL, which is need of the hour.