The iron export protein ferroportin 1 is differentially expressed in mouse macrophage populations and is present in the mycobacterial-containing phagosome
Open accessAbstract
Intracellular pathogens, including Mycobacterium tuberculosis, obtain iron from the host for their survival. Ferroportin 1 (FPN1; SLC40A1) is the sole iron exporter from mammalian cells and is expressed in the duodenum and macrophages. In the present study, we show that FPN1 mRNA levels in the mouse macrophage cell line RAW264.7 are synergistically induced by treatment with live or γ-irradiated M. tuberculosis and IFN-γ. FPN1 mRNA levels were also induced by Mycobacterium avium and IFN-γ in RAW264.7 cells and the mouse alveolar macrophage cell line AMJ2-C8. Treatment of mouse resident peritoneal macrophages with M. tuberculosis and IFN-γ resulted in a sixfold increase in FPN1 mRNA expression. In contrast, M. tuberculosis and IFN-γ inhibited FPN1 mRNA expression in bone marrow-derived macrophages and lung macrophages, which have high basal levels of FPN1 mRNA expression. Using confocal microscopy, FPN1 protein localized rapidly to M. tuberculosis phagosomes after infection in RAW264.7 macrophages. In RAW264.7 cells expressing wild-type natural resistance-associated macrophage protein 1 (Nramp1Gly169), FPN1 and Nramp1 partially colocalized in late endosomes/lysosomes prior to infection. After 2 h of infection, Nramp1 and FPN1 were present in M. tuberculosis phagosomes. Our studies provide evidence for transcriptional regulation of FPN1 by pathogenic mycobacteria and IFN-γ, which is dependent on the macrophage type. The trafficking of FPN1 to the M. tuberculosis phagosome suggests that it is involved in regulating iron availability to the mycobacteria in this locale.
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Mycobacteria circumvent iron-withholding defenses by directly modulating ferroportin expression.
“Mycobacteria circumvent these iron-withholding defenses by directly modulating ferroportin expression (Van Zandt et al., 2008).”
From Iron in infection and immunity (2013) · cites this paper as Van Zandt et al., 2008
Ferroportin rapidly localizes to Mycobacterium tuberculosis-infected phagolysosomes, resulting in iron efflux from that compartment.
“Additionally, ferroportin rapidly localizes to Mtb-infected phagolysosomes, resulting in iron efflux from this cellular compartment.”
From Iron in infection and immunity (2013) · cites this paper as Van Zandt et al., 2008
Ferroportin is found in the membrane of the M. tuberculosis-containing phagosome, which can be referred to a direct stimulatory effect of M. tuberculosis on ferroportin transcription.
“Ferroportin was found in the membrane of the M. tuberculosis-containing phagosome, which can be referred to a direct stimulatory effect of M. tuberculosis on ferroportin transcription.”
From Macrophage defense mechanisms against intracellular bacteria (2015) · cites this paper as [172]
When expressed in phagosomes, FPN can reduce iron supply to pathogens in that compartment, as shown in vitro for Mycobacteria infection.
“When expressed in phagosomes FPN can reduce Fe supply to pathogens in this subcellular compartment, as shown in vitro for Mycobacteria infection [101] (Fig 3).”
From The Iron age of host–microbe interactions (2015) · cites this paper as [101]
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- Authors
- Van Zandt, K. E., Sow, F. B., Florence, W. C., Zwilling, B. S., Satoskar, A. R., Schlesinger, L. S., & Lafuse, W. P.
- Affiliations
- Department of Microbiology, The Ohio State University , Columbus, Ohio , USA
- The Ohio State University (US)
- Corresponding author
- Lafuse, William P
- Venue
- Journal of Leukocyte Biology
- Publisher
- Oxford University Press (OUP)
- Published
- 2008-06-27
- Volume
- 84
- Issue
- 3
- Pages
- 689-700
- ISSN
- 0741-5400 (ISSN-L)
- 1938-3673
- PMC
- PMC2516892
- OpenAlex
- W2107596308
- Cited by
- 74
- References
- 20
- Citations by year
- 2026: 3 · 2024: 3 · 2023: 2 · 2022: 2 · 2021: 2 · 2020: 8 · 2019: 1 · 2018: 7 · 2017: 5 · 2016: 4 · 2015: 8 · 2014: 8 · 2013: 6 · 2012: 4
- FWCI
- 2.39
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Leukocyte Biology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (AI45673, DK57667)
- Topics
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Health Sciences › Medicine › Infectious Diseases › Tuberculosis Research and Epidemiology
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Ferroptosis and cancer prognosis
- Keywords
- ferroportin 1, SLC40A1, Mycobacterium tuberculosis, macrophages, iron export, phagosome, NRAMP1, interferon-gamma, transcriptional regulation, Mycobacterium avium, host-pathogen interaction, iron acquisition, RAW 264.7 macrophages, alveolar macrophages, bone marrow-derived macrophages, peritoneal macrophages
- MeSH terms
- Ferroportin, Natural Resistance-associated Macrophage Protein 1, Animals, Bone Marrow, Cells, Cultured, Fluorescent Antibody Technique, Gene Expression Regulation, Immunity, Innate, Interferon-gamma, Iron, Lung, Lysosomes, Male, Mice, Inbred C57BL, Mycobacterium avium, Mycobacterium tuberculosis, Phagosomes, Endosomes, Tuberculosis, Blotting, Western, Macrophages, Alveolar, Macrophages, Peritoneal, Cation Transport Proteins, Mice
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