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Cited by 23Tuberculosis Research and EpidemiologyIron Metabolism and DisordersImmune responses and vaccinations

The expression of ferritin, lactoferrin, transferrin receptor and solute carrier family 11A1 in the host response to BCG-vaccination and Mycobacterium tuberculosis challenge

Thom, R.E., Elmore, M.J., Williams, A., Andrews, S.C., Drobniewski, F., Marsh, P.D., Tree, J.A.·2012·Vaccine
DOI 10.1016/j.vaccine.2012.03.008
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Abstract

Iron is an essential cofactor for both mycobacterial growth during infection and for a successful protective immune response by the host. The immune response partly depends on the regulation of iron by the host, including the tight control of expression of the iron-storage protein, ferritin. BCG vaccination can protect against disease following Mycobacterium tuberculosis infection, but the mechanisms of protection remain unclear. To further explore these mechanisms, splenocytes from BCG-vaccinated guinea pigs were stimulated ex vivo with purified protein derivative from M. tuberculosis and a significant down-regulation of ferritin light- and heavy-chain was measured by reverse-transcription quantitative-PCR (P≤0.05 and ≤0.01, respectively). The mechanisms of this down-regulation were shown to involve TNFα and nitric oxide. A more in depth analysis of the mRNA expression profiles, including genes involved in iron metabolism, was performed using a guinea pig specific immunological microarray following ex vivo infection with M. tuberculosis of splenocytes from BCG-vaccinated and naïve guinea pigs. M. tuberculosis infection induced a pro-inflammatory response in splenocytes from both groups, resulting in down-regulation of ferritin (P≤0.05). In addition, lactoferrin (P≤0.002), transferrin receptor (P≤0.05) and solute carrier family 11A1 (P≤0.05), were only significantly down-regulated after infection of the splenocytes from BCG-vaccinated animals. The results show that expression of iron-metabolism genes is tightly regulated as part of the host response to M. tuberculosis infection and that BCG-vaccination enhances the ability of the host to mount an iron-restriction response which may in turn help to combat invasion by mycobacteria.

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  • In BCG-infected splenocytes, a NO-dependent reduction in the expression of ferritin and TfR was observed.

    “a recent investigation in BCG-infected splenocytes indicated a NO-dependent reduction in the expression of ferritin and TfR (180).”

    From Macrophage defense mechanisms against intracellular bacteria (2015) · cites this paper as [180]

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Authors
Thom, R. E., Elmore, M. J., Williams, A., Andrews, S. C., Drobniewski, F., Marsh, P. D., & Tree, J. A.
Affiliations
  • University of Reading (GB)
  • Queen Mary University of London (GB)
Corresponding author
Thom, R.E.
ORCID
Venue
Vaccine
Publisher
Elsevier BV
Published
2012-05
Volume
30
Issue
21
Pages
3159-3168
ISSN
0264-410X (ISSN-L)
DOI
10.1016/j.vaccine.2012.03.008
OpenAlex
W2057237340
Cited by
23
References
45
Citations by year
2026: 3 · 2025: 1 · 2022: 2 · 2021: 2 · 2020: 2 · 2019: 2 · 2018: 1 · 2017: 2 · 2016: 3 · 2015: 1 · 2014: 4
FWCI
1.10
Type
journal article
Language
en
Open access
closed
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Vaccine (publishedVersion)
  • PubMed (publishedVersion)
  • CentAUR (University of Reading) (submittedVersion)
Topics
  • Health Sciences › Medicine › Infectious Diseases › Tuberculosis Research and Epidemiology
  • Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
  • Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
Keywords
BCG vaccination, Mycobacterium tuberculosis, iron metabolism, ferritin, lactoferrin, transferrin receptor, SLC11A1, iron limitation, host response to infection, TNF-α, nitric oxide, splenocytes, guinea pig, purified protein derivative, gene expression profiling
MeSH terms
Natural Resistance-associated Macrophage Protein 1, Animals, BCG Vaccine, Ferritins, Guinea Pigs, Iron, Lactoferrin, Mycobacterium tuberculosis, Receptors, Transferrin, Tuberculosis, Gene Expression Profiling, Cation Transport Proteins, Microarray Analysis, Real-Time Polymerase Chain Reaction

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