Role of Ferroportin in Macrophage-Mediated Immunity

Johnson, Erin E.; Sandgren, Andreas; Cherayil, Bobby J.; Murray, Megan; Wessling-Resnick, Marianne

doi:10.1128/iai.00498-10

Cited by 68Iron Metabolism and DisordersTuberculosis Research and EpidemiologyImmune Response and Inflammation

Role of Ferroportin in Macrophage-Mediated Immunity

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Johnson, Erin E., Sandgren, Andreas, Cherayil, Bobby J., Murray, Megan, Wessling-Resnick, Marianne·2010·Infection and Immunity

DOI 10.1128/iai.00498-10PMC PMC2981308

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Abstract

Perturbations in iron metabolism have been shown to dramatically impact host response to infection. The most common inherited iron overload disorder results from defects in the HFE gene product, a major histocompatibility complex class I-like protein that interacts with transferrin receptors. HFE-associated hemochromatosis is characterized by abnormally high levels of the iron efflux protein ferroportin. In this study, J774 murine macrophages overexpressing ferroportin were used to investigate the influence of iron metabolism on the release of nitric oxide (NO) in response to infection. Overexpression of ferroportin significantly impaired intracellular Mycobacterium tuberculosis growth during early stages of infection. When challenged with lipopolysaccharide (LPS) or M. tuberculosis infection, control macrophages increased NO synthesis, but macrophages overexpressing ferroportin had significantly impaired NO production in response to LPS or M. tuberculosis . Increased NO synthesis in control cells was accompanied by increased iNOS mRNA and protein, while upregulation of iNOS protein was markedly reduced when J744 cells overexpressing ferroportin were challenged with LPS or M. tuberculosis , thus limiting the bactericidal activity of these macrophages. The proinflammatory cytokine gamma interferon reversed the inhibitory effect of ferroportin overexpression on NO production. These results suggest a novel role for ferroportin in attenuating macrophage-mediated immune responses.

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Ferroportin-mediated iron export is effective in macrophages infected with M. tuberculosis.
“This mechanism has also proven to be effective in macrophages infected with M. tuberculosis (183).”
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Overexpression of FPN1 decreases survival of the intracellular pathogen Mycobacterium tuberculosis.
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From Iron in immune cell function and host defense (2021) · cites this paper as [161]
Ferroportin overexpressing macrophages also have reduced iNOS production and phagocytic ability, suggesting that depletion of intracellular iron stores may interfere with macrophage effector functions.
“Interestingly, ferroportin overexpressing macrophages also have reduced inducible nitric oxide synthase (iNOS) production and phagocytic ability, suggesting that depletion of intracellular iron stores may interfere with macrophage effector functions [52].”
From Hepcidin and Host Defense against Infectious Diseases (2015) · cites this paper as [52]
Ferroportin overexpressing macrophages have lower mycobacterial burden as compared to normal macrophages when infected with M. tuberculosis in vitro.
“Ferroportin overexpressing macrophages have lower mycobacterial burden as compared to normal macrophages when infected with M. tuberculosis in vitro [52].”
From Hepcidin and Host Defense against Infectious Diseases (2015) · cites this paper as [52]
The detrimental effect of hepcidin in intracellular infections is not supported by in vivo data.
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From Hepcidin and Host Defense against Infectious Diseases (2015) · cites this paper as [52]

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Ferroportin Modulates Macrophage‐Mediated Immune Responses
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Authors: Johnson, E. E., Sandgren, A., Cherayil, B. J., Murray, M., & Wessling-Resnick, M.
Affiliations: Harvard University (US)
Massachusetts General Hospital (US)
Department of Genetics and Complex Diseases, Harvard School of Public Health, Boston, Massachusetts 02115
ORCID: Johnson, Erin E.
Sandgren, Andreas
Cherayil, Bobby J.
Murray, Megan
Venue: Infection and Immunity
Publisher: American Society for Microbiology
Published: 2010-12
Volume: 78
Issue: 12
Pages: 5099-5106
ISSN: 0019-9567 (ISSN-L)
1098-5522
DOI: 10.1128/iai.00498-10
PMC: PMC2981308
OpenAlex: W2118427665
Cited by: 68
References: 59
Citations by year: 2026: 1 · 2025: 3 · 2024: 3 · 2023: 5 · 2022: 3 · 2021: 3 · 2020: 7 · 2019: 3 · 2018: 6 · 2017: 4 · 2016: 4 · 2015: 6 · 2014: 4 · 2013: 7 · 2012: 6
FWCI: 3.21
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: journals.asm.org/non-commercial-tdm-license (tdm)
Locations: Infection and Immunity (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
Funders: National Institutes of Health (5t32es007155-24, ES014638)
National Institute of Allergy and Infectious Diseases (R21AI068077, R21 AI06519)
National Institute of Diabetes and Digestive and Kidney Diseases (R01DK064750, T90DK070078, P30DK043351, P30DK040561)
National Institute of Environmental Health Sciences (T32-ES007155, R01ES014638)
Topics: Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
Health Sciences › Medicine › Infectious Diseases › Tuberculosis Research and Epidemiology
Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Keywords: ferroportin, iron metabolism, nitric oxide production, inducible nitric oxide synthase, Mycobacterium tuberculosis, lipopolysaccharide, interferon-gamma, iron efflux, bacterial clearance, J774 macrophages
MeSH terms: Ferroportin, Animals, Cell Line, Gene Expression Regulation, Immunity, Cellular, Macrophages, Mycobacterium tuberculosis, Nitric Oxide, Tuberculosis, Blotting, Western, Polymerase Chain Reaction, NF-kappa B, Nitric Oxide Synthase, Cation Transport Proteins, Mice

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Role of Ferroportin in Macrophage-Mediated Immunity

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