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Subverted transferrin trafficking in Leishmania-infected macrophages
V M Borges1, M A Vannier-Santos, W de Souza
1Laboratório de Ultraestrutura Celular Hertha Meyer, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Brasil.
Parasitology Research
|October 31, 1998
Summary
Leishmania parasites hijack host cell transferrin (HTf) trafficking for iron acquisition. Infected macrophages show distinct HTf pathways, with parasites internalizing HTf for survival and replication.
Area of Science:
- Cell Biology
- Parasitology
- Immunology
Background:
- Human transferrin (HTf) transports iron, essential for cell function.
- Leishmania parasites infect macrophages, requiring iron for survival.
- Understanding host-pathogen interactions is crucial for disease control.
Purpose of the Study:
- To investigate the intracellular trafficking of human transferrin (HTf) in Leishmania-infected macrophages.
- To determine if Leishmania amastigotes utilize host HTf for iron uptake.
- To elucidate the role of HTf in the survival of intracellular Leishmania.
Main Methods:
- Utilized gold-conjugated HTf and bovine serum albumin (BSA) for pulse-chase experiments.
- Employed light and electron microscopy with immunolabeling techniques.
- Conducted HTf-fluorescein isothiocyanate (FITC) assays and double-staining assays.
Main Results:
- Leishmania-infected macrophages exhibit distinct HTf trafficking compared to uninfected cells.
- HTf is delivered to the parasitophorous vacuole and associates with amastigote surfaces.
- Intracellular amastigotes internalize HTf, sorting it to parasite endosomal-lysosomal compartments.
- HoloHTf treatment enhances parasite survival, unlike apoHTf.
Conclusions:
- Leishmania amastigotes exploit and subvert the host cell's endocytic system.
- Transferrin-bound iron plays a significant role in the outcome of Leishmania infection.
- Targeting HTf uptake could be a potential therapeutic strategy against leishmaniasis.