CoChat
Sign Up
Cited by 96Tuberculosis Research and EpidemiologyIron Metabolism and DisordersImmune responses and vaccinations

The natural resistance-associated macrophage protein and susceptibility to intracellular pathogens

Open access
Bellamy, Richard·1999·Microbes and Infection
DOI 10.1016/s1286-4579(99)80010-0
Open this paper in CoChat — free account

Abstract

Over 20 years ago it was recognised that murine susceptibility to several antigenically unrelated pathogens was influenced by a host genetic factor. Linkage studies suggested that Lsh, Ity, and Bcg, the leishmania-, salmonella-, and mycobacteria-susceptibility genes, may be one gene, located on mouse chromosome 1. A reverse genetics strategy identified a candidate gene, Nramp1, which was expressed only in reticuloendothelial cells. A single nonconservative amino acid substitution was found to correlate with the susceptibility genotype in 27 inbred mouse strains. The production of an Nramp1 gene-disrupted mouse and a transgenic mouse, which restored the resistance genotype, conclusively proved that Nramp1 is the Bcg/Lsh/Ity gene. The Nramp family includes genes expressed in both prokaryotic and eukaryotic species. These genes have provided clues to the possible function of Nramp1. The ubiquitously expressed gene Nramp2 is an Fe(2+) transporter and a mutation in this gene causes microcytic anaemia in mice and rats. The functions of Nramp1 and its human homologue, NRAMP1, remain unknown, though it is hypothesised that they may regulate the intraphagosomal concentration of Fe(2+) and/or other cations. The identification of polymorphisms in the human NRAMP1 gene has facilitated studies on the relevance of this gene to human mycobacterial susceptibility. NRAMP1 variant alleles are strongly associated with tuberculosis, indicating that this is an important mycobacterial-susceptibility gene in humans and confirming the usefulness of this mouse model in the study of human infectious disease susceptibility.

Integrity signals

Registry

Crossref · 10.1016/s1286-4579(99)80010-0

Cites

59 of 59 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

We couldn’t retrieve this paper’s full text, so its claims and self-check weren’t run. The registry and citation checks still apply.

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?

  • The importance of NRAMP1 functionality for resistance to infection against several mycobacteria but not M. tuberculosis has been shown in mice.

    “Although the importance of NRAMP1 functionality for resistance to infection against several mycobacteria but not M. tuberculosis has been shown in mice, an increased susceptibility to tuberculosis in high endemic areas has a mild association with specific polymorphisms in the NRAMP1 gene (226, 227).”

    From Macrophage defense mechanisms against intracellular bacteria (2015) · cites this paper as [226]

  • Increased susceptibility to tuberculosis in high endemic areas has a mild association with specific polymorphisms in the NRAMP1 gene.

    “Although the importance of NRAMP1 functionality for resistance to infection against several mycobacteria but not M. tuberculosis has been shown in mice, an increased susceptibility to tuberculosis in high endemic areas has a mild association with specific polymorphisms in the NRAMP1 gene (226, 227).”

    From Macrophage defense mechanisms against intracellular bacteria (2015) · cites this paper as [226]

  • Patients with polymorphisms in the regulatory region of NRAMP1 that lower its expression are at higher risk for infection with M. tuberculosis.

    “patients with polymorphisms in the regulatory region of NRAMP1 that lower its expression are at a higher risk for infection with M. tuberculosis”

    From Iron in immune cell function and host defense (2021) · cites this paper as [28]

Cites

Flagged first, then by citations

2 of the 61 references couldn’t be matched to a known paper.

Cited by

Sorted by citations

Related

Authors
Bellamy, R.
Affiliations
University Hospital of Wales (GB)
Corresponding author
Bellamy, Richard
Venue
Microbes and Infection
Publisher
Elsevier BV
Published
1999-01
Volume
1
Issue
1
Pages
23-27
ISSN
1286-4579 (ISSN-L)
DOI
10.1016/s1286-4579(99)80010-0
OpenAlex
W2032022850
Cited by
96
References
61
Citations by year
2022: 2 · 2020: 2 · 2019: 2 · 2018: 2 · 2017: 1 · 2016: 4 · 2015: 1 · 2014: 2 · 2013: 2 · 2012: 6
FWCI
4.46
Type
journal article
Language
en
Open access
Licence
Locations
  • Microbes and Infection (publishedVersion)
  • PubMed (publishedVersion)
Funders
Wellcome Trust
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
NRAMP1, NRAMP, host genetic susceptibility, intracellular pathogens, mouse chromosome 1, reticuloendothelial cells, DMT1, iron transport, tuberculosis susceptibility, inbred mouse strains, genetic polymorphism, transgenic mice
MeSH terms
Natural Resistance-associated Macrophage Protein 1, Solute Carrier Family 11, Member 2, Animals, Carrier Proteins, Disease Susceptibility, Humans, Immunity, Innate, Macrophages, Membrane Proteins, Cation Transport Proteins, Iron-Binding Proteins, Mice, Rats

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