Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD, USA.
Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD, USA; Department of Animal and Avian Sciences, University of Maryland, College Park, MD, USA; Department of Physiology, Institute of Biosciences, University of São Paulo, São Paulo, SP, Brazil.
Int J Parasitol. 2019 May;49(6):423-427. doi: 10.1016/j.ijpara.2019.02.002. Epub 2019 Mar 22.
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.
利什曼原虫质膜转运蛋白利什曼铁调节蛋白 1（LIR1）促进铁的输出，是寄生虫毒力所必需的。通过调节巨噬细胞中的铁含量，我们研究了 LIR1 调节利什曼原虫亚马逊亚种感染性的宿主部位。在骨髓来源的巨噬细胞中，LIR1 缺失突变体在缺乏血红素的培养基中感染时表现出反常的毒力增加，而在相同条件下野生型生长受到抑制。在感染前将阳离子化铁蛋白加载到巨噬细胞的内吞途径中，可逆转血红素耗尽对两种菌株的影响。因此，LIR1 通过保护寄生虫免受吞噬空泡内铁积累引起的毒性，有助于利什曼原虫的毒力。
