Anti-leishmanial therapy: Caught between drugs and immune targets

Leishmaniasis is an enigmatic disease that has very restricted options for chemotherapy and none for prophylaxis. As a result, deriving therapeutic principles for curing the disease has been a major objective in Leishmania research for a long time. Leishmania is a protozoan parasite that lives within macrophages by subverting or switching cell signaling to the pathways that ensure its intracellular survival. Therefore, three groups of molecules aimed at blocking or eliminating the parasite, at least, in principle, include blockers of macrophage receptor- Leishmania ligand interaction, macrophage-activating small molecules, peptides and cytokines, and signaling inhibitors or activators. Macrophages also act as an antigen-presenting cell, presenting antigen to the antigen-specific T cells to induce activation and differentiation of the effector T cell subsets that either execute or suppress anti-leishmanial functions. Three groups of therapeutic principles targeting this sphere of Leishmania-macrophage interaction include antibodies that block pro-leishmanial response of T cells, ligands that activate anti-leishmanial T cells and the antigens for therapeutic vaccines. Besides these, prophylactic vaccines have been in clinical trials but none has succeeded so far. Herein, we have attempted to encompass all these principles and compose a comprehensive review to analyze the feasibility and adoptability of different therapeutics for leishmaniasis.