Modulation of iron homeostasis in macrophages by bacterial intracellular pathogens

Pan, Xin; Tamilselvam, Batcha; Hansen, Eric J; Daefler, Simon

doi:10.1186/1471-2180-10-64

Cited by 69Iron Metabolism and DisordersBacterial Genetics and BiotechnologyEscherichia coli research studies

Modulation of iron homeostasis in macrophages by bacterial intracellular pathogens

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Pan, Xin, Tamilselvam, Batcha, Hansen, Eric J, Daefler, Simon·2010·BMC Microbiology

DOI 10.1186/1471-2180-10-64PMC PMC2838877

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Abstract

Background: Intracellular bacterial pathogens depend on acquisition of iron for their success as pathogens. The host cell requires iron as an essential component for cellular functions that include innate immune defense mechanisms. The transferrin receptor TfR1 plays an important part for delivering iron to the host cell during infection. Its expression can be modulated by infection, but its essentiality for bacterial intracellular survival has not been directly investigated. Results: We identified two distinct iron-handling scenarios for two different bacterial pathogens. Francisella tularensis drives an active iron acquisition program via the TfR1 pathway program with induction of ferrireductase (Steap3), iron membrane transporter Dmt1, and iron regulatory proteins IRP1 and IRP2, which is associated with a sustained increase of the labile iron pool inside the macrophage. Expression of TfR1 is critical for Francisella's intracellular proliferation. This contrasts with infection of macrophages by wild-type Salmonella typhimurium , which does not require expression of TfR1 for successful intracellular survival. Macrophages infected with Salmonella lack significant induction of Dmt1, Steap3, and IRP1, and maintain their labile iron pool at normal levels. Conclusion: The distinction between two different phenotypes of iron utilization by intracellular pathogens will allow further characterization and understanding of host-cell iron metabolism and its modulation by intracellular bacteria.

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During infection with intracellular pathogenic microorganisms, iron is required by both the host cell and the pathogen that inhabits the host cell.
“During infection with intracellular pathogenic microorganisms, the element iron is required by both the host cell and the pathogen that inhabits the host cell.”
From Strategies of intracellular pathogens for obtaining iron from the environment (2015) · cites this paper as [12]
The success of intracellular parasites seems to be related mainly to their ability to take up Fe from the protein Tf.
“The success of intracellular parasites seems to be related mainly to their ability to take up Fe from the protein Tf [12].”
From Strategies of intracellular pathogens for obtaining iron from the environment (2015) · cites this paper as [12]

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Self-citation
Effect of the expression of transferrin receptor 1 on the invasion of Francisella into macrophages
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Regulation of macrophage iron homeostasis is associated with the localization of bacteria
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Authors: Pan, X., Tamilselvam, B., Hansen, E. J., & Daefler, S.
Affiliations: Icahn School of Medicine at Mount Sinai (US)
Corresponding author: Daefler, Simon
ORCID: Pan, Xin
Venue: BMC Microbiology
Publisher: Springer Science and Business Media LLC
Published: 2010-02-25
Volume: 10
Issue: 1
Pages: 64-64
ISSN: 1471-2180 (ISSN-L)
DOI: 10.1186/1471-2180-10-64
PMC: PMC2838877
OpenAlex: W2121253747
Cited by: 69
References: 55
Citations by year: 2025: 2 · 2024: 2 · 2023: 2 · 2022: 6 · 2021: 2 · 2020: 8 · 2019: 3 · 2018: 6 · 2017: 1 · 2016: 6 · 2015: 7 · 2014: 8 · 2013: 4 · 2012: 6
FWCI: 3.20
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
Locations: BMC Microbiology (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders: U.S. Public Health Service
National Institute of Allergy and Infectious Diseases (P0AI55637)
Topics: Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Escherichia coli research studies
Keywords: iron homeostasis, macrophages, intracellular bacterial pathogens, transferrin receptor 1, Francisella tularensis, Salmonella typhimurium, iron acquisition, labile iron pool, host-pathogen interaction, innate immunity
MeSH terms: Animals, Cell Line, Francisella tularensis, Gene Expression Regulation, Homeostasis, Iron, Macrophages, Receptors, Transferrin, Salmonella typhimurium, Up-Regulation, Cytoplasmic Vesicles, Intracellular Space, Cell Growth Processes, Mice, Metabolic Networks and Pathways

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Modulation of iron homeostasis in macrophages by bacterial intracellular pathogens

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