The DOI matches its Crossref record; 50 of the 52 references it cites were found in a registry or an index.
Expression and localization of hepcidin in macrophages: a role in host defense against tuberculosis
Abstract
Hepcidin is an antimicrobial peptide produced by the liver in response to inflammatory stimuli and iron overload. Hepcidin regulates iron homeostasis by mediating the degradation of the iron export protein ferroportin 1, thereby inhibiting iron absorption from the small intestine and release of iron from macrophages. Here, we examined the expression of hepcidin in macrophages infected with the intracellular pathogens Mycobacterium avium and Mycobacterium tuberculosis. Stimulation of the mouse RAW264.7 macrophage cell line and mouse bone marrow-derived macrophages with mycobacteria and IFN-γ synergistically induced high levels of hepcidin mRNA and protein. Similar results were obtained using the human THP-1 monocytic cell line. Stimulation of macrophages with the inflammatory cytokines IL-6 and IL-β did not induce hepcidin mRNA expression. Iron loading inhibited hepcidin mRNA expression induced by IFN-γ and M. avium, and iron chelation increased hepcidin mRNA expression. Intracellular protein levels and secretion of hepcidin were determined by a competitive chemiluminescence ELISA. Stimulation of RAW264.7 cells with IFN-γ and M. tuberculosis induced intracellular expression and secretion of hepcidin. Furthermore, confocal microscopy analyses showed that hepcidin localized to the mycobacteria-containing phagosomes. As hepcidin has been shown to possess direct antimicrobial activity, we investigated its activity against M. tuberculosis. We found that hepcidin inhibited M. tuberculosis growth in vitro and caused structural damage to the mycobacteria. In summary, our data show for the first time that hepcidin localizes to the phagosome of infected, IFN-γ-activated cells and has antimycobacterial activity.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“However, M. tuberculosis can also stimulate the formation of hepcidin in MΦs and subvert the stimulation of ferroportin-mediated iron excess and ensure iron retention within the MO (197).”
From Macrophage defense mechanisms against intracellular bacteria (2015) · cites this paper as [197]
In the citing paper
“Similarly, very high concentrations of hepcidin have been shown to inhibit M. tuberculosis growth in vitro [32], but it is unknown whether these concentrations are relevant to in vivo infections.”
From Hepcidin and Host Defense against Infectious Diseases (2015) · cites this paper as [32]
In the citing paper
“This effect has been demonstrated convincingly in vitro”
From Hepcidin and Host Defense against Infectious Diseases (2015) · cites this paper as [32]
In the citing paper
“hepcidin induces iron accumulation in macrophages”
From Hepcidin and Host Defense against Infectious Diseases (2015) · cites this paper as [32]
In the citing paper
“may be detrimental in defense against pathogens that occupy this intracellular niche”
From Hepcidin and Host Defense against Infectious Diseases (2015) · cites this paper as [32]
In the citing paper
“but is not supported by in vivo data [32,39–43,49–55]”
From Hepcidin and Host Defense against Infectious Diseases (2015) · cites this paper as [32]
In the citing paper
“Detrimental, by promoting sequestration of iron in macrophages”
From Hepcidin and Host Defense against Infectious Diseases (2015) · cites this paper as [32]
Citations
Cites
Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2−ΔΔCT Method
Livak, K. J., & Schmittgen, T. D. (2001) · Methods · doi:10.1006/meth.2001.1262 · Cited by 180,860
Hepcidin Regulates Cellular Iron Efflux by Binding to Ferroportin and Inducing Its Internalization
Nemeth, E., Tuttle, M. S., Powelson, J., Vaughn, M. B., Donovan, A., Ward, D. M., Ganz, T., & Kaplan, J. (2004) · Science · doi:10.1126/science.1104742 · Cited by 4,803
NITRIC OXIDE AND MACROPHAGE FUNCTION
MacMicking, J. D., Xie, Q. W., & Nathan, C. (1997) · Annual Review of Immunology · doi:10.1146/annurev.immunol.15.1.323 · Cited by 4,245
Nemeth, E., Rivera, S., Gabayan, V., Keller, C., Taudorf, S., Pedersen, B. K., & Ganz, T. (2004) · Journal of Clinical Investigation · doi:10.1172/jci200420945 · Cited by 2,650 · cited 8×
“Hepcidin is produced rapidly by the liver in mice in response to inflammatory stimuli, LPS, Freund adjuvant, and turpentine [29, 32, 33, 40].”
BackgroundInfluentialAn essential role for interferon gamma in resistance to Mycobacterium tuberculosis infection.
Flynn, J. L., Chan, J., Triebold, K. J., Dalton, D. K., Stewart, T. A., & Bloom, B. R. (1993) · The Journal of Experimental Medicine · doi:10.1084/jem.178.6.2249 · Cited by 2,468
Hepcidin, a urinary antimicrobial peptide synthesized in the liver
Park, C. H., Valore, E. V., Waring, A. J., & Ganz, T. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m008922200 · Cited by 2,168
Disseminated tuberculosis in interferon gamma gene-disrupted mice.
Cooper, A. M., Dalton, D. K., Stewart, T. A., Griffin, J. P., Russell, D. G., & Orme, I. M. (1993) · The Journal of Experimental Medicine · doi:10.1084/jem.178.6.2243 · Cited by 1,987
Pigeon, C., Ilyin, G., Courselaud, B., Leroyer, P., Turlin, B., Brissot, P., & Loréal, O. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m008923200 · Cited by 1,697
Hepcidin, a key regulator of iron metabolism and mediator of anemia of inflammation
Ganz, T. (2003) · Blood · doi:10.1182/blood-2003-03-0672 · Cited by 1,544
Transcriptional Adaptation of Mycobacterium tuberculosis within Macrophages
Schnappinger, D., Ehrt, S., Voskuil, M. I., Liu, Y., Mangan, J. A., Monahan, I. M., Dolganov, G., Efron, B., Butcher, P. D., Nathan, C., et al. (2003) · The Journal of Experimental Medicine · doi:10.1084/jem.20030846 · Cited by 1,420
Flagged first, then by citations
2 of the 52 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Items 201–228 of 228
Crichton, R. R. (2016) · Wiley eBooks · doi:10.1002/9781118925645.ch12
Running head: TLR2/6 mediated hepcidin-independent hypoferremia
Guida, C., Altamura, S., Klein, F. A., Galy, B., Boutros, M., Ulmer, A. J., Hentze, M. W., & Muckenthaler, M. U. (2016)
BASIC N EUROSCIENCES, G ENETICS A ND I MMUNOLOGY - R EVIEW A RTICLE
WardRobert, R. J., Crichton, R. R., Corte, D., & Dexter, T. M. (2011)
Comparison of Serum Levels of Hepcidin in Brucellosis Patients and Healthy Individuals
Hashemi, S., Tayebinia, H., Esna‐Ashari, F., & Gorgani, F. N. (2017) · مجله پزشکی بالینی ابن سینا · doi:10.21859/ajcm.24.3.199
IN TRANSLATION Molecular Mechanisms of Hepcidin Regulation: Implications for the Anemia of CKD
Babitt, J. L., & Lin, H. Y.-F. (2010)
The role of hepcidin in iron metabolism in athletes
Bajić, Z., Ponorac, N., & Matavulj, A. (2019) · Fizicka kultura · doi:10.5937/fizkul1902206b
Serum Hepcidin and Prohepcidin Levels in Nonfebrile and Febrile Neutropenia
Koluman, B. Ü., Avcı, E., Güler, N., Çağlıyan, G. A., & Şenol, H. (2021) · Journal of College of Physicians And Surgeons Pakistan · doi:10.29271/jcpsp.2021.11.1303
Validity of Serum And Urinary Hepcidin As Biomarkers of Late-Onset Sepsis of Premature InfantsPreprint
Sherbiny, H. S., Mostafa, H. A., Halm, M. M. A.-E., El‐Shal, A. S., Kamal, N. M., Khan, H. Y., & Ali, A. S. A. (2021) · Research Square · doi:10.21203/rs.3.rs-1053179/v1
貴重書紹介 アンドレアス・ヴェサリウス『人体の構造についての七つの書』--1543年,バーゼル,オポリヌス書店刊 (蔵書の玉手箱)
鈴木, 秀. (2000) · 図書の譜
Identification and analysis of genetic and chemical modulators of iron metabolism
Hawula, Z. J. (2021) · Queensland University of Technology · doi:10.5204/thesis.eprints.225904 · Cited by 1
Iron Uptake in Host Defense Against Pneumonia
Michels, K. R. (2017) · doi:10.18130/v3465h
KillingMycobacterium tuberculosis In Vitro: What Model Systems Can Teach Us
Keiser, T. L., & Purdy, G. E. (2017) · ASM Press eBooks · doi:10.1128/9781555819569.ch25
A study of an Incidence of tuberculosis is linked to elevated hepcidin at HIV diagnosis
Saxena, P., Kumar, S. M., & Pooja, P. (2023) · Cardiometry · doi:10.18137/cardiometry.2022.25.14411443
Wang, R., Liu, X., Chen, J., Wang, Y., Han, Q., & Wang, X. (2024) · SSRN Electronic Journal · doi:10.2139/ssrn.4883743
The Fight for Iron: A Central Theme in Host-Pathogen Interactions
Hamad, M. A. (2025) · Springer eBooks · doi:10.1007/978-981-96-1305-2_11
Wang, R., Liu, X., Wang, Y., Xie, Q., Guo, C., Yuan, M., & Wang, X. (2025) · SSRN Electronic Journal · doi:10.2139/ssrn.5364347
Fang, Q., Wang, R., Liu, X., Wang, Y., Xie, Q., Guo, C., Yuan, M., & Wang, X. (2025) · Molecular Immunology · doi:10.1016/j.molimm.2025.12.004
Oh, T. K., Song, K.-H., & Song, I.-A. (2021) · Figshare · doi:10.6084/m9.figshare.14955860
Oh, T. K., Song, K.-H., & 송인애 (2021) · Figshare · doi:10.6084/m9.figshare.14955857
Oh, T. K., Song, K.-H., & Song, I.-A. (2021) · Figshare · doi:10.6084/m9.figshare.14955854
Simakova, M. A., Zhilenkova, Y. I., Алексеевна, З. Е., Вавилова, Т. В., & Моисеева, О. М. (2026) · Russian Journal of Cardiology · doi:10.15829/1560-4071-2025-6475
The organoid revolution to assess mycobacterial pulmonary infections
Leon‐Icaza, S. A. (2022) · theses.fr (ABES) · doi:10.70675/6e135d5fzb953z4ffcz9041z2684784040ad
Pritam, P., Das, S., Behera, S. K., SAHOO, M., Subudhi, L., Mohapatra, S., & Panda, A. K. (2026) · Frontiers in Antibiotics · doi:10.3389/frabi.2026.1769369
Siddalingaiah, H. S. (2026) · Research Square · doi:10.21203/rs.3.rs-10908347/v1
Devan, A. R., Babu, P., Kumar, G. B., Nair, B. G., Pillai, A. B., & Madhavan, A. (2026) · Pharmaceutics · doi:10.3390/pharmaceutics18101326
Metadata
- Authors
- Sow, F. B., Florence, W. C., Satoskar, A. R., Schlesinger, L. S., Zwilling, B. S., & Lafuse, W. P.
- Affiliations
- The Ohio State University (US)
- Corresponding author
- Lafuse, William P
- Venue
- Journal of Leukocyte Biology
- Publisher
- Oxford University Press (OUP)
- Published
- 2007-07-03
- Volume
- 82
- Issue
- 4
- Pages
- 934-945
- ISSN
- 0741-5400 (ISSN-L)
- 1938-3673
- OpenAlex
- W2107072141
- Cited by
- 229
- References
- 52
- Citations by year
- 2026: 6 · 2025: 7 · 2024: 10 · 2023: 6 · 2022: 12 · 2021: 19 · 2020: 7 · 2019: 12 · 2018: 9 · 2017: 14 · 2016: 10 · 2015: 17 · 2014: 12 · 2013: 18 · 2012: 13
- FWCI
- 9.16
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Leukocyte Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (RO1DK-57667)
- Topics
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Health Sciences › Medicine › Infectious Diseases › Tuberculosis Research and Epidemiology
- Life Sciences › Immunology and Microbiology › Microbiology › Antimicrobial Peptides and Activities
- Keywords
- hepcidin, macrophages, tuberculosis, Mycobacterium tuberculosis, Mycobacterium avium, iron homeostasis, ferroportin 1, interferon-gamma, antimicrobial activity, phagosome, host defense, iron chelation, iron loading
- MeSH terms
- Animals, Cell Line, Gene Expression Regulation, Homeostasis, Humans, Immunity, Innate, Interferon-gamma, Intestinal Absorption, Iron, Iron Chelating Agents, Liver, Mycobacterium avium, Mycobacterium tuberculosis, Phagosomes, RNA, Messenger, Tuberculosis, Iron Overload, Antimicrobial Cationic Peptides, Mice, Hepcidins
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
