Journal
INTERNATIONAL JOURNAL FOR PARASITOLOGY
Volume 49, Issue 6, Pages 423-427Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.ijpara.2019.02.002
Keywords
Heme; Cationic ferritin; Amastigotes; Endocytic pathway; Virulence; Drug target
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Funding
- National Institutes of Health, USA [RO1 AI067979]
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The Leishmania plasma membrane transporter Leishmania Iron Regulator 1 (LIR1) facilitates iron export and is required for parasite virulence. By modulating macrophage iron content, we investigated the host site where LIR1 regulates Leishmania amazonensis infectivity. In bone marrow-derived macrophages, LIR1 null mutants demonstrated a paradoxical increase in virulence during infections in heme-depleted media, while wild-type growth was inhibited under the same conditions. Loading the endocytic pathway of macrophages with cationized ferritin prior to infection reversed the effect of heme depletion on both strains. Thus, LIR1 contributes to Leishmania virulence by protecting the parasites from toxicity resulting from iron accumulation inside parasitophorous vacuoles. (C) 2019 Australian Society for Parasitology. Published by Elsevier Ltd. All rights reserved.
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