ArticlePLoS pathogens2013
Granzyme A produced by γ(9)δ(2) T cells induces human macrophages to inhibit growth of an intracellular pathogen.
Article in PLoS pathogens, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.
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Who cites it
75 citing papers in PubMed, 110 citations in OpenAlex.
- Functional, Antigen-Specific Stem Cell Memory (TFrontiers in immunology · 2018Trial
- Human lung γδ T cells maintain functionality during inflammatory lung disease.bioRxiv : the preprint server for biology · 2026Article
- Review
- The mechanism regulating the cytotoxicity of γδ T cells activated by mycobacterium tuberculosis heat-resistant antigen based on RNA-seq analysis.Frontiers in immunology · 2026Article
- Vγ9Vδ2 T cells in tuberculosis: protective immunity and translational perspectives.Frontiers in immunology · 2026Review
- Leveraging a synthetic biology approach to enhance BCG-mediated expansion of Vγ9Vδ2 T cells.PloS one · 2026Article
- Characterization and anti-tuberculosis effects of γδ T cells expanded and activated byVirulence · 2025Review
- Cytotoxic granules and effector molecules from immune cells in tuberculosis: Mechanisms of host defense and therapeutic potential.Virulence · 2025Review
- Hyperglycemic milieu impairs Vγ9Vδ2 T cell functions in tuberculosis patients and prolongs M.tb negative conversion time.iScience · 2025Article
- Vγ9Vδ2 T cells expanded with vitamin C combined with HMBPPFrontiers in cellular and infection microbiology · 2025Article
- Single-cell analysis of peripheral blood and pleural effusion reveals functional diversity of γδ T cells in tuberculosis infection.Frontiers in immunology · 2025Article
- A Novel Role for γδ T Cells in Protection Against Severe Melioidosis.American journal of respiratory cell and molecular biology · 2024Article
- Assays for AssessingPathogens (Basel, Switzerland) · 2024Article
- Tristetraprolin mediates immune evasion of mycobacterial infection in macrophages.FASEB bioAdvances · 2024Article
- Analysis of the components of Mycobacterium tuberculosis heat-resistant antigen (Mtb-HAg) and its regulation of γδ T-cell function.Cellular & molecular biology letters · 2024Article
- Human Vγ9Vδ2 T cells exhibit antifungal activity againstMicrobiology spectrum · 2024Article
- Homodimeric Granzyme A Opsonizes Mycobacterium tuberculosis and Inhibits Its Intracellular Growth in Human Monocytes via Toll-Like Receptor 4 and CD14.The Journal of infectious diseases · 2024Article
- γδ T cells: origin and fate, subsets, diseases and immunotherapy.Signal transduction and targeted therapy · 2023Review
- Review
- Phenotypic and functional characterization of pharmacologically expanded Vγ9Vδ2 T cells in pigtail macaques.iScience · 2023Article
15 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
Human γ(9)δ(2) T cells potently inhibit pathogenic microbes, including intracellular mycobacteria, but the key inhibitory mechanism(s) involved have not been identified. We report a novel mechanism involving the inhibition of intracellular mycobacteria by soluble granzyme A. γ(9)δ(2) T cells produced soluble factors that could pass through 0.45 µm membranes and inhibit intracellular mycobacteria in human monocytes cultured below transwell inserts. Neutralization of TNF-α in co-cultures of infected monocytes and γ(9)δ(2) T cells prevented inhibition, suggesting that TNF-α was the critical inhibitory factor produced by γ(9)δ(2) T cells. However, only siRNA- mediated knockdown of TNF-α in infected monocytes, but not in γ(9)δ(2) T cells, prevented mycobacterial growth inhibition. Investigations of other soluble factors produced by γ(9)δ(2) T cells identified a highly significant correlation between the levels of granzyme A produced and intracellular mycobacterial growth inhibition. Furthermore, purified granzyme A alone induced inhibition of intracellular mycobacteria, while knockdown of granzyme A in γ(9)δ(2) T cell clones blocked their inhibitory effects. The inhibitory mechanism was independent of autophagy, apoptosis, nitric oxide production, type I interferons, Fas/FasL and perforin. These results demonstrate a novel microbial defense mechanism involving granzyme A-mediated triggering of TNF-α production by monocytes leading to intracellular mycobacterial growth suppression. This pathway may provide a protective mechanism relevant for the development of new vaccines and/or immunotherapies for macrophage-resident chronic microbial infections.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.