ArticleThe Journal of clinical investigation2021
Integrated transcriptomic analysis of human tuberculosis granulomas and a biomimetic model identifies therapeutic targets.
Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 43 citations in OpenAlex.
- Single-cell and spatial profiling highlights TB-induced myofibroblasts as drivers of lung pathology.The Journal of experimental medicine · 2026Article
- Insights into the host response to 'dormant' Mycobacterium tuberculosis utilizing 'Vitamin C-induced dormant Mtb' THP-1 cell infection model.BMC genomics · 2026Article
- Species-specific iNOS expression distinguishes epithelial and myeloid IFNγ responses in tuberculosis.bioRxiv : the preprint server for biology · 2026Article
- MMPs and NETs are detrimental in CNS-tuberculosis with MMP Inhibition in CNS-tuberculosis mice improving survival.Journal of neuroinflammation · 2025Article
- Article
- Unravelling the transcriptome of the human tuberculosis lesion and its clinical implications.Nature communications · 2025Article
- Endoplasmic Reticulum Stress in Tuberculosis: Molecular Bases and Pathophysiological Implications in the Immunopathogenesis of the Disease.International journal of molecular sciences · 2025Review
- Distinguishing multiple roles of T cell and macrophage involvement in determining lymph node fates during Mycobacterium tuberculosis infection.PLoS computational biology · 2025Article
- Distinguishing multiple roles of T cell and macrophage involvement in determining lymph node fates during Mycobacterium tuberculosis infection.PLoS computational biology · 2025Article
- FAM46C Expression Sensitizes Multiple Myeloma Cells to PF-543-Induced Cytotoxicity.Biomolecules · 2025Article
- A bovine pulmosphere model and multiomics reveal early host response signature in tuberculosis.Communications biology · 2025Article
- Article
- Identification of ferroptosis-related key genes in tuberculosis by bioinformatics methods.AMB Express · 2025Article
- 3D Hydrogel Culture System Recapitulates Key Tuberculosis Phenotypes and Demonstrates Pyrazinamide Efficacy.Advanced healthcare materials · 2025Article
- Overview of multi-omics approaches for pulmonary sarcoidosis.EC pulmonology and respiratory medicine · 2025Article
- Microenvironments of tuberculous granuloma: advances and opportunities for therapy.Frontiers in immunology · 2025Review
- Spatial transcriptomic validation of a biomimetic model of fibrosis enables re-evaluation of a therapeutic antibody targeting LOXL2.Cell reports. Medicine · 2024Article
- B cell heterogeneity in human tuberculosis highlights compartment-specific phenotype and functional roles.Communications biology · 2024Article
- 3D human tissue models and microphysiological systems for HIV and related comorbidities.Trends in biotechnology · 2024Review
- Next-Gen Dual Transcriptomics for Adult Extrapulmonary Tuberculosis Biomarkers and Host-Pathogen Interplay in Human Cells: A Strategic Review.Indian journal of microbiology · 2024Review
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Authors and funding
15 authors at 5 institutions in 4 countries.
Funding
Abstract
Tuberculosis (TB) is a persistent global pandemic, and standard treatment for it has not changed for 30 years. Mycobacterium tuberculosis (Mtb) has undergone prolonged coevolution with humans, and patients can control Mtb even after extensive infection, demonstrating the fine balance between protective and pathological host responses within infected granulomas. We hypothesized that whole transcriptome analysis of human TB granulomas isolated by laser capture microdissection could identify therapeutic targets, and that comparison with a noninfectious granulomatous disease, sarcoidosis, would identify disease-specific pathological mechanisms. Bioinformatic analysis of RNAseq data identified numerous shared pathways between TB and sarcoidosis lymph nodes, and also specific clusters demonstrating TB results from a dysregulated inflammatory immune response. To translate these insights, we compared 3 primary human cell culture models at the whole transcriptome level and demonstrated that the 3D collagen granuloma model most closely reflected human TB disease. We investigated shared signaling pathways with human disease and identified 12 intracellular enzymes as potential therapeutic targets. Sphingosine kinase 1 inhibition controlled Mtb growth, concurrently reducing intracellular pH in infected monocytes and suppressing inflammatory mediator secretion. Immunohistochemical staining confirmed that sphingosine kinase 1 is expressed in human lung TB granulomas, and therefore represents a host therapeutic target to improve TB outcomes.
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Registered trials
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.