IRONy OF FATE: role of iron-mediated ROS in Leishmania differentiation

• Iron uptake regulates differentiation of Leishmania promastigotes into virulent amastigote forms.
• Iron uptake is essential for FeSOD activation and generation of H2O2.
• H2O2 promotes differentiation of avirulent promastigotes into virulent amastigotes.

The protozoan parasite Leishmania experiences extreme environmental changes as it alternates between insect and mammalian hosts. In some species, differentiation of insect promastigotes into mammalian-infective amastigotes is induced by elevated temperature and low pH, conditions found within macrophage parasitophorous vacuoles (PVs). However, the signaling events controlling amastigote differentiation remain poorly understood. Recent studies revealed a novel role for iron uptake in orchestrating the differentiation of amastigotes, through a mechanism that involves production of reactive oxygen species (ROS) and is independent from pH and temperature changes. ROS are generally thought to be deleterious for pathogens, but it is becoming increasingly apparent that they can also function as signaling molecules regulating Leishmania differentiation, in a process that is tightly controlled by iron availability.