ArticlePLoS pathogens2016
The L-Arginine Transporter Solute Carrier Family 7 Member 2 Mediates the Immunopathogenesis of Attaching and Effacing Bacteria.
Article in PLoS pathogens, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 27 citations in OpenAlex.
- Diverse infections transcriptionally reprogram the intestinal epithelium and epithelial-immune cell interactions.Nature immunology · 2026Article
- Regulation of Inducible Nitric Oxide Synthase (NOS2) Expression in Healthy and Inflamed Bowel: A Narrative Review.International journal of molecular sciences · 2026Review
- Pancreatic islet α cell function and proliferation require the arginine transporter SLC7A2.The Journal of clinical investigation · 2026Article
- CBP/p300 is critical for the expansion and maintenance of functional pancreatic α cell mass.Nature communications · 2026Article
- Age-dependent immune responses and resident cell dynamics in young mice following pneumonia.iScience · 2026Article
- Understanding the Mechanistic Connection between Dysbiosis and Polyamine Regulation in Oral and Intestinal Inflammation- Role of Tregs and Th17 Cells.Journal of cellular immunology · 2026Article
- Loss of SETD2-mediated H3K36me3 Drives CD8Research (Washington, D.C.) · 2026Article
- From metabolic antagonism to homeostatic restoration: rewiring hepatic stellate cell bioenergetics for liver fibrosis reversal.Frontiers in medicine · 2026Review
- Genome-wide association study and transcriptomic analysis reveal the crucial role ofFrontiers in immunology · 2025Article
- Immune signature of gene expression pattern shared by autism spectrum disorder and Huntington's disease.IBRO neuroscience reports · 2024Article
- Myeloid deletion of talin-1 reduces mucosal macrophages and protects mice from colonic inflammation.Scientific reports · 2023Article
- Soluble adenylyl cyclase contributes to imiquimod-mediated inflammation and is a potential therapeutic target in psoriasis.Experimental dermatology · 2023Article
- Barley Leaf AmelioratesNutrients · 2023Article
- Arginine metabolism regulates the pathogenesis of inflammatory bowel disease.Nutrition reviews · 2023Article
- Integrated transcriptomic and metabolomic analysis reveals the metabolic programming of GM-CSF- and M-CSF- differentiated mouse macrophages.Frontiers in immunology · 2023Article
- CircSLC7A2 protects against osteoarthritis through inhibition of the miR-4498/TIMP3 axis.Cell proliferation · 2021Article
- l-Arginine sensing regulates virulence gene expression and disease progression in enteric pathogens.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Characterisation of genes differentially expressed in macrophages by virulent and attenuated Mycobacterium tuberculosis through RNA-Seq analysis.Scientific reports · 2019Article
- Loss of solute carrier family 7 member 2 exacerbates inflammation-associated colon tumorigenesis.Oncogene · 2019Article
- Dietary Arginine Regulates Severity of Experimental Colitis and Affects the Colonic Microbiome.Frontiers in cellular and infection microbiology · 2019Article
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
Abstract
Solute carrier family 7 member 2 (SLC7A2) is an inducible transporter of the semi-essential amino acid L-arginine (L-Arg), which has been implicated in immune responses to pathogens. We assessed the role of SLC7A2 in murine infection with Citrobacter rodentium, an attaching and effacing enteric pathogen that causes colitis. Induction of SLC7A2 was upregulated in colitis tissues, and localized predominantly to colonic epithelial cells. Compared to wild-type mice, Slc7a2-/-mice infected with C. rodentium had improved survival and decreased weight loss, colon weight, and histologic injury; this was associated with decreased colonic macrophages, dendritic cells, granulocytes, and Th1 and Th17 cells. In infected Slc7a2-/-mice, there were decreased levels of the proinflammatory cytokines G-CSF, TNF-α, IL-1α, IL-1β, and the chemokines CXCL1, CCL2, CCL3, CCL4, CXCL2, and CCL5. In bone marrow chimeras, the recipient genotype drove the colitis phenotype, indicative of the importance of epithelial, rather than myeloid SLC7A2. Mice lacking Slc7a2 exhibited reduced adherence of C. rodentium to the colonic epithelium and decreased expression of Talin-1, a focal adhesion protein involved in the attachment of the bacterium. The importance of SLC7A2 and Talin-1 in the intimate attachment of C. rodentium and induction of inflammatory response was confirmed in vitro, using conditionally-immortalized young adult mouse colon (YAMC) cells with shRNA knockdown of Slc7a2 or Tln1. Inhibition of L-Arg uptake with the competitive inhibitor, L-lysine (L-Lys), also prevented attachment of C. rodentium and chemokine expression. L-Lys and siRNA knockdown confirmed the role of L-Arg and SLC7A2 in human Caco-2 cells co-cultured with enteropathogenic Escherichia coli. Overexpression of SLC7A2 in human embryonic kidney cells increased bacterial adherence and chemokine expression. Taken together, our data indicate that C. rodentium enhances its own pathogenicity by inducing the expression of SLC7A2 to favor its attachment to the epithelium and thus create its ecological niche.
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