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- W4384501786 abstract "Leishmania parasites are heavily dependent on efficient iron acquisition from a tightly regulated host iron pool for survival and virulence. Prior studies uncovered multiple strategies adopted by the parasite to hijack the iron-regulatory network of macrophages. Despite these extensive studies with infected macrophages, there is limited knowledge of the effect of Leishmania infection on systemic iron homeostasis. This issue is particularly relevant for Leishmania major, which causes localized skin infection with minimal lymphatic spread. We show for the first time that L. major infection in the mouse footpad induced influx of iron at the site of infection through blood with simultaneous upregulation of transferrin receptor 1 (TfR1) and downregulation of phagolysosomal iron exporter Nramp1 expression in the footpad tissue. Interestingly, localized L. major infection had far-reaching effects beyond the infection site triggering anemia-like symptoms. This was evident from depleted physiological iron stores from the liver and bone marrow as well as reduced hemoglobin levels and deformed erythrocytes. The infected mice also developed splenomegaly with signs of splenic stress erythropoiesis as indicated by upregulation of several erythroid-related genes. These observations prompted us to provide oral iron supplementations to the L. major infected mice, which resulted in a drastic reduction of the parasite load and restoration of iron homeostasis." @default.
- W4384501786 created "2023-07-18" @default.
- W4384501786 creator A5036528485 @default.
- W4384501786 creator A5043595661 @default.
- W4384501786 date "2023-08-01" @default.
- W4384501786 modified "2023-09-26" @default.
- W4384501786 title "Localized Leishmania major infection disrupts systemic iron homeostasis that can be controlled by oral iron supplementation" @default.
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- W4384501786 doi "https://doi.org/10.1016/j.jbc.2023.105064" @default.
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