Figure 2. Leishmania must acquire iron from the host to survive inside PVs.

Within PVs of macrophages Leishmania upregulates an iron transport machinery that allows it to compete with the host iron transporter Nramp1 for iron. Intracellular amastigotes of Leishmania express on their plasma membrane the ferric iron reductase LFR1, which converts Fe³⁺ that enters the macrophage as a complex with transferrin into Fe²⁺, the soluble iron form. Fe²⁺ is then translocated across the membrane by LIT1, a ferrous iron transporter that is also upregulated in the iron-poor environment of the PV. When higher concentrations of iron are available inside the parasitophorous vacuole, low affinity iron transporters can compensate for the absence of LHR1 and LIT1, promoting parasite replication. Abbreviation: PV, parasitophorous vacuole.