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

Authors
  • Bisti, S
  • Konidou, G
  • Papageorgiou, F
  • Milon, G
  • Boelaert, J R
  • Soteriadou, K
Type
Published Article
Journal
European journal of immunology
Publication Date
Dec 01, 2000
Volume
30
Issue
12
Pages
3732–3740
Identifiers
PMID: 11169417
Source
Medline
License
Unknown

Abstract

We previously established that Leishmania promastigotes express a transferrin receptor and that iron chelators inhibit promastigote growth in vitro. Thus, 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 106 stationary phase promastigotes. Treatment of mice with desferrioxamine resulted in a slight delay of the development of cutaneous lesions. In contrast and unexpectedly, systemic iron delivery, at early time points of parasite delivery, significantly limited footpad pathology. Accordingly, parasite loads at the site of parasite delivery, the draining lymph node, liver and spleen were significantly reduced in iron-loaded mice. Importantly, the "protective" effect of iron delivery correlated with the presence, at the site of inoculation, of lower levels of IL-4 and IL-10 transcripts while both IFN-gamma and inducible nitric oxide synthase transcripts were at higher levels. The presence of more 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 that alter the iron status of the host at early time points of parasite delivery.

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