The outcome of Leishmania major experimental infection in BALB/c mice can be modulated by exogenously delivered iron

We previously established that Leishmania promastigotes express a transferr in receptor and that iron chelators inhibit promastigote growth in vitro. T hus, we were interested in modulating the vertebrate host iron pool and to monitor whether such changes will affect the outcome of L. major infection in BALB/c mice, inoculated in the footpad with 10(6) stationary phase proma stigotes. Treatment of mice with desferrioxamine resulted in a slight delay of the development of cutaneous lesions. In contrast and unexpectedly syst emic iron delivery, at early time points of parasite delivery, significantl y limited footpad pathology. Accordingly, parasite loads at the site of par asite delivery, the draining lymph node, liver and spleen were significantl y reduced in iron-loaded mice. Importantly, the "protective" effect of iron delivery correlated with the presence, at the site of inoculation, of lowe r levels of IL-4 and IL-10 transcripts while both IFN-gamma and inducible n itric oxide synthase transcripts were at higher levels. The presence of mor e type 1 cytokine transcripts was further supported by the increased levels of IgG2a in their sera. These data strongly suggest that susceptibility to L. major as assessed in the footpad model is modifiable by interventions t hat alter the iron status of the host at early time points of parasite deli very.