ArticlePLoS neglected tropical diseases2009
Local suppression of T cell responses by arginase-induced L-arginine depletion in nonhealing leishmaniasis.
Article in PLoS neglected tropical diseases, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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Who cites it
62 citing papers in PubMed, 101 citations in OpenAlex.
- Combination of single-cell and bulk RNA-seq reveals changes in the immune landscape in osteomyelitis.Frontiers in immunology · 2026Article
- The regulatory role and mechanism of energy metabolism and immune response in head and neck cancer.Genes & diseases · 2025Review
- Immunotherapeutic Strategies as Potential Treatment Options for Cutaneous Leishmaniasis.Vaccines · 2024Review
- Streptococcal Arginine Deiminase Inhibits T Lymphocyte Differentiation In Vitro.Microorganisms · 2023Article
- Amino acid metabolism in immune cells: essential regulators of the effector functions, and promising opportunities to enhance cancer immunotherapy.Journal of hematology & oncology · 2023Review
- The Role of Extracellular Vesicles in Metabolic Reprogramming of the Tumor Microenvironment.Cells · 2022Review
- Polyamine Metabolism inMedical sciences (Basel, Switzerland) · 2022Review
- Macrophage: A Cell With Many Faces and Functions in Tuberculosis.Frontiers in immunology · 2022Review
- Potent but transient immunosuppression of T-cells is a general feature of CD71Communications biology · 2021Article
- Promotion of Anti-Tuberculosis Macrophage Activity by L-Arginine in the Absence of Nitric Oxide.Frontiers in immunology · 2021Article
- Immunotherapy in Myeloproliferative Diseases.Cells · 2020Review
- Differential Regulation of l-Arginine Metabolism through Arginase 1 during Infection with Leishmania mexicana Isolates Obtained from Patients with Localized and Diffuse Cutaneous Leishmaniasis.Infection and immunity · 2020Article
- Myeloid Cell-Derived Arginase in Cancer Immune Response.Frontiers in immunology · 2020Review
- Small extracellular vesicles containing arginase-1 suppress T-cell responses and promote tumor growth in ovarian carcinoma.Nature communications · 2019Observational
- IL-33 induces immunosuppressive neutrophils via a type 2 innate lymphoid cell/IL-13/STAT6 axis and protects the liver against injury in LCMV infection-induced viral hepatitis.Cellular & molecular immunology · 2019Article
- Model-based Evaluation of Gene Expression Changes in Response toGene regulation and systems biology · 2019Review
- Probiotic Exopolysaccharide Protects against SystemicInfection and immunity · 2019Article
- Arginase-1 Expression in Myeloid Cells Regulates Staphylococcus aureus Planktonic but Not Biofilm Infection.Infection and immunity · 2018Article
- Arginase1 Deficiency in Monocytes/Macrophages Upregulates Inducible Nitric Oxide Synthase To Promote Cutaneous Contact Hypersensitivity.Journal of immunology (Baltimore, Md. : 1950) · 2017Article
- Arginase activity in pathogenic and non-pathogenic species of Leishmania parasites.PLoS neglected tropical diseases · 2017Article
2 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 6 institutions in 4 countries.
Funding
Abstract
The balance between T helper (Th) 1 and Th2 cell responses is a major determinant of the outcome of experimental leishmaniasis, but polarized Th1 or Th2 responses are not sufficient to account for healing or nonhealing. Here we show that high arginase activity, a hallmark of nonhealing disease, is primarily expressed locally at the site of pathology. The high arginase activity causes local depletion of L-arginine, which impairs the capacity of T cells in the lesion to proliferate and to produce interferon-gamma, while T cells in the local draining lymph nodes respond normally. Healing, induced by chemotherapy, resulted in control of arginase activity and reversal of local immunosuppression. Moreover, competitive inhibition of arginase as well as supplementation with L-arginine restored T cell effector functions and reduced pathology and parasite growth at the site of lesions. These results demonstrate that in nonhealing leishmaniasis, arginase-induced L-arginine depletion results in impaired T cell responses. Our results identify a novel mechanism in leishmaniasis that contributes to the failure to heal persistent lesions and suggest new approaches to therapy.
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