Cross-talk between Leishmania and its mammalian host-cell: insights from Chemical genetics and antimony-resistant field
Protozoan parasites of the genus Leishmania are the causative agents of a wide variety of diseases that range from self-healing cutaneous or mucocutaneous lesions to a visceral form of the disease in which parasites disseminate to internal organs. This diversity is due to heterogeneity both among Leishmania species and the host immune response. Leishmaniasis is one of the most significant neglected tropical diseases, with an estimated 12 million people infected.
The parasites are transmitted to mammalian hosts through the bite of phlebotomine sandflies. Parasites that develop in the mid-gut of the flies, called promastigotes, are flagellated and extracellular. Promastigotes progress through distinct stages of differentiation to become the infectious metacyclics that upon injection into the mammalian bloodstream are rapidly phagocytosed by macrophages, where they differentiate into the amastigote form. Amastigotes multiply in the macrophage parasitophorous vacuole, leading to destruction of the host cell and release of free amastigotes into the bloodstream, where they are capable of infecting new phagocytic cells.
Treatment for Leishmaniasis relies on chemotherapy: sodium stibogluconate (SSG) has been the first line treatment for several decades but it is now being replaced by miltefosine, aphotericin B or paromomycin; no other drugs are in the pipeline.