Related Experiment Video
Updated: May 3, 2026
Quantification of Intracellular Growth Inside Macrophages is a Fast and Reliable Method for Assessing the Virulence of Leishmania Parasites
Published on: March 16, 2018
Leishmania-mediated inhibition of iron export promotes parasite replication in macrophages
Rym Ben-Othman1, Andrew R Flannery1, Danilo C Miguel1
1Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, Maryland, United States of America.
Abstract:
Leishmania parasites infect macrophages, cells that play an important role in organismal iron homeostasis. By expressing ferroportin, a membrane protein specialized in iron export, macrophages release iron stored intracellularly into the circulation. Iron is essential for the intracellular replication of Leishmania, but how the parasites compete with the iron export function of their host cell is unknown. Here, we show that infection with Leishmania amazonensis inhibits ferroportin expression in macrophages. In a TLR4-dependent manner, infected macrophages upregulated transcription of hepcidin, a peptide hormone that triggers ferroportin degradation. Parasite replication was inhibited in hepcidin-deficient macrophages and in wild type macrophages overexpressing mutant ferroportin that is resistant to hepcidin-induced degradation. Conversely, intracellular growth was enhanced by exogenously added hepcidin, or by expression of dominant-negative ferroportin. Importantly, dominant-negative ferroportin and macrophages from flatiron mice, a mouse model for human type IV hereditary hemochromatosis, restored the infectivity of mutant parasite strains defective in iron acquisition. Thus, inhibition of ferroportin expression is a specific strategy used by L. amazonensis to inhibit iron export and promote their own intracellular growth.
Insights
Leishmania parasites manipulate macrophage iron export by inhibiting ferroportin. This strategy, dependent on hepcidin, allows parasites to acquire essential iron for intracellular growth.
Area of Science:
- Immunology
- Parasitology
- Cell Biology
Background:
- Macrophages are key to iron homeostasis, exporting iron via ferroportin.
- Leishmania parasites require iron for replication within macrophages.
- The mechanism by which Leishmania competes for iron is not fully understood.
Purpose of the Study:
- To investigate how Leishmania amazonensis manipulates host macrophage iron metabolism.
- To determine the role of ferroportin and hepcidin in Leishmania infection.
Main Methods:
- Assessing ferroportin expression in infected macrophages.
- Analyzing hepcidin and Toll-like receptor 4 (TLR4) involvement.
- Evaluating parasite replication in macrophages with altered ferroportin or hepcidin levels.
- Utilizing hepcidin-deficient and flatiron mice models.
Main Results:
- Leishmania amazonensis infection downregulates macrophage ferroportin expression.
- Infected macrophages upregulate hepcidin transcription in a TLR4-dependent manner, leading to ferroportin degradation.
- Inhibition of ferroportin or hepcidin deficiency impairs parasite replication.
- Exogenous hepcidin or dominant-negative ferroportin enhances parasite growth.
Conclusions:
- Leishmania amazonensis actively inhibits host iron export by downregulating ferroportin.
- This mechanism, involving hepcidin, ensures iron availability for parasite replication.
- Targeting ferroportin is a critical strategy for Leishmania survival and proliferation within macrophages.
Related Concept Videos
01:22Microbial Interactions: Parasitism
01:28Fungal Phylum Microsporidia