Role of iron in intracellular growth of Trypanosoma cruzi

Abstract

Host hypoferremic responses occur during infection with T. cruzi, presumably through the transfer of Fe to the sites of intracellular parasite replication. Depletion of host intracellular Fe stores reduces parasite pathogenicity. It has therefore been hypothesized that T. cruzi requires Fe for optimal growth in host cells and that, unlike extracellular pathogens, T. cruzi may benefit from host hypoferremic responses. These hypotheses were examined by the in vitro infection of peritoneal macrophages with T. cruzi. Various doses of desferrioxamine or referrated desferrioxamine were added to the culture medium, and parasite growth was monitored. The influence of treatment on uninfected macrophage morphology, function and Fe content was also verified. Desferrioxamine reduced the rate of amastigote replication in a dose-dependent fashion; referrated desferrioxamine did not. The Fe content of desferrioxamine-treated macrophages was decreased by 55% without provoking significant morphologcial or functional changes. Thus, amastigotes used host cell Fe stores for optimal growth, and desferrioxamine reduced growth by depleting host cell Fe. Hence, it was suggested that depletion of host intracellular Fe stores may protect against T. cruzi and, furthermore, that host responses which transfer Fe to the intracellular sites of T. cruzi replication may enhance parasite pathogenicity.