Slc11a1, Formerly Nramp1, Is Expressed in Dendritic Cells and Influences Major Histocompatibility Complex Class II Expression and Antigen-Presenting Cell Function
Open accessAbstract
Solute carrier family 11 member a1 (Slc11a1; formerly Nramp1) encodes a late endosomal/lysosomal protein/divalent cation transporter that regulates iron homeostasis in macrophages. During macrophage activation, Slc11a1 has multiple pleiotropic effects on gene regulation and function, including gamma interferon-induced class II expression and antigen-presenting cell function. The wild-type allele at Slc11a1 has been associated with a bias in Th1 cell function in vivo, which is beneficial in resistance to infection against intracellular macrophage pathogens but detrimental in contributing to development of type 1 diabetes. The extent to which this depends on macrophage versus dendritic cell (DC) function is not known. Here we show that Slc11a1 is expressed in late endosomes and/or lysosomes of CD11c+DCs. DCs from mutant and congenic wild-type mice upregulate interleukin-12 (IL-12) and IL-10 mRNA in response to lipopolysaccharide (LPS) stimulation, but the ratio of IL-10 to IL-12 is higher in unstimulated DCs and DCs stimulated for 15 h with LPS from mutant mice than from wild-type mice. DCs from wild-type mice upregulate major histocompatibility complex class II in response to LPS more efficiently than DCs from mutant mice. Unstimulated DCs from wild-type and mutant mice present ovalbumin (OVA) peptide with an efficiency equivalent to that of an OVA-specific CD4 T-cell line, but DCs from wild-type mice are more efficient at processing and presenting OVA or Leishmania activator of cell kinase (LACK) protein to OVA- and LACK-specific T cells. These data indicate that wild-type Slc11a1 expressed in DCs may play a role both in determining resistance to infectious disease and in susceptibility to autoimmune disease such as type 1 diabetes.
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Nramp1 cation transport function is directly linked to antimicrobial activity of macrophages and DCs.
“Its cation transport function is directly linked to the antimicrobial activity of macrophages and DCs [74, 163, 219].”
From “Pumping iron”—how macrophages handle iron at the systemic, microenvironmental, and cellular levels (2017) · cites this paper as [219]
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- Authors
- Stober, C. B., Brode, S., White, J. K., Popoff, J.-F., & Blackwell, J. M.
- Affiliations
- University of Cambridge (GB)
- Cambridge Institute for Medical Research and Department of Medicine, Wellcome Trust/MRC Building, University of Cambridge School of Clinical Medicine, Addenbrookes Hospital, Hills Road, Cambridge CB2 2XY, United Kingdom
- Corresponding author
- Blackwell, Jenefer M.
- Venue
- Infection and Immunity
- Publisher
- American Society for Microbiology
- Published
- 2007-10
- Volume
- 75
- Issue
- 10
- Pages
- 5059-5067
- ISSN
- 0019-9567 (ISSN-L)
- 1098-5522
- PMC
- PMC2044529
- OpenAlex
- W2146904676
- Cited by
- 68
- References
- 53
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 1 · 2023: 3 · 2022: 2 · 2020: 4 · 2019: 1 · 2018: 6 · 2017: 1 · 2016: 3 · 2015: 4 · 2014: 4 · 2013: 7 · 2012: 2
- FWCI
- 2.45
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Infection and Immunity (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- UWA Profiles and Research Repository (UWA) (submittedVersion)
- Funders
- Wellcome Trust (065642)
- National Institute of Allergy and Infectious Diseases (R01AI067874)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- SLC11A1, NRAMP1, dendritic cells, MHC class II expression, antigen presentation, iron homeostasis, macrophages, IL-12, IL-10, lipopolysaccharide, type 1 diabetes, Leishmania, ovalbumin, late endosomes, lysosomes
- MeSH terms
- Natural Resistance-associated Macrophage Protein 1, Animals, Histocompatibility Antigens Class II, Antigens, Protozoan, Cells, Cultured, Dendritic Cells, Flow Cytometry, Gene Expression Regulation, Leishmania, Lipopolysaccharides, Lysosomes, Major Histocompatibility Complex, Mice, Mutant Strains, Ovalbumin, Endosomes, RNA, Messenger, Protozoan Proteins, Bias, Interleukin-10, Antigen Presentation, Microscopy, Confocal, Interleukin-12, Reverse Transcriptase Polymerase Chain Reaction, Cation Transport Proteins, Mice
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