Solute carrier 11A1 is expressed by innate lymphocytes and augments their activation
Open accessAbstract
Solute carrier 11A1 (SLC11A1) is a divalent ion transporter formerly known as the natural resistance-associated macrophage protein (NRAMP1) and the Bcg/Lsh/Ity locus. SLC11A1 was thought to be exclusively expressed in monocyte/macrophages and to have roles in phagosome maturation and cell activation. We characterized the expression of SLC11A1 in the majority of human and bovine γδ T cells and NK cells and in human CD3(+)CD45RO(+) T cells. Consistent with a role for iron-dependent inhibition of protein tyrosine phosphatases, SLC11A1(+) lymphocytes were more prone to activation and retained tyrosine phosphorylation. Transfection of SLC11A1 into a human γδ T cell-like line rendered the cells more prone to activation. Nonadherent splenocytes from wild-type mice expressed significantly greater IFN-γ compared with cells from Sv/129 (SLC11A1(-/-)) mice. Our data suggest that SLC11A1 has a heretofore unknown role in activation of a large subset of innate lymphocytes that are critical sources of IFN-γ. SLC11A1(+) animals have enhanced innate IFN-γ expression in response to Salmonella infection compared with SLC11A1(-) mice, which include commonly used inbred laboratory mice. Expression of SLC11A1 in innate lymphocytes and its role in augmenting their activation may account for inconsistencies in studies of innate lymphocytes in different animal models.
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Many effectors of microbial iron withdrawal have direct or indirect impact on acquired immunity, such as the function of lymphocyte subsets.
“Furthermore, many effectors of microbial iron withdrawal have direct or indirect impact on acquired immunity such as the function of lymphocyte subsets (Dai et al., 2009;Hedges et al., 2013;Lee et al., 2020;Stober et al., 2007).”
From Iron in infection and immunity (2020) · cites this paper as Hedges et al., 2013
The Introduction describes SLC11A1 as an iron transporter that may restrict iron availability to internalized bacteria. The Results (‘Role of iron in activation of lymphocytes’) show that iron availability affects activation of innate lymphocytes. This supports an example of an iron-related effector affecting a lymphocyte subset, but the paper does not establish that many such effectors affect acquired immunity. (LLM, conf=0.85)
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- Authors
- Hedges, J. F., Kimmel, E., Snyder, D. T., Jerome, M., & Jutila, M. A.
- Affiliations
- Montana State University (US)
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2013-04
- Volume
- 190
- Issue
- 8
- Pages
- 4263-4273
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- PMC
- PMC3622125
- OpenAlex
- W2101934558
- Cited by
- 39
- References
- 69
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 2 · 2023: 4 · 2022: 7 · 2021: 3 · 2020: 3 · 2019: 5 · 2018: 3 · 2017: 3 · 2016: 3 · 2015: 1 · 2014: 2
- FWCI
- 1.11
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of General Medical Sciences (GM-103500, P30GM110732, P20GM103500)
- National Center for Research Resources (P20RR020185, RR 020185)
- National Center for Complementary and Integrative Health (AT0004986-01, P01AT004986)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Immune Cell Function and Interaction
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- SLC11A1, NRAMP1, innate lymphoid cells, γδ T cells, natural killer cells, CD45RO+ memory T cells, lymphocyte activation, tyrosine phosphorylation, interferon-gamma, salmonellosis, innate immunity
- MeSH terms
- Natural Resistance-associated Macrophage Protein 1, Animals, Cattle, Humans, Immunity, Innate, Lymphocyte Activation, Phosphorylation, Tyrosine, Up-Regulation, T-Lymphocyte Subsets, Receptors, Antigen, T-Cell, gamma-delta, Protein Tyrosine Phosphatases, Mice, Knockout, Cation Transport Proteins, Mice, Mice, 129 Strain
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