ArticlePLoS pathogens2011
Early secreted antigen ESAT-6 of Mycobacterium tuberculosis promotes protective T helper 17 cell responses in a toll-like receptor-2-dependent manner.
Article in PLoS pathogens, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 95 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
95 citing papers in PubMed, 154 citations in OpenAlex.
- Exploring microorganism-host interactions: Emerging organoid models and analytical approaches.mLife · 2026Review
- Immunoregulation by ESAT-6: From Pathogenesis of Tuberculosis to Potential Anti-Inflammatory and Anti-Rejection Application.Pharmaceuticals (Basel, Switzerland) · 2025Review
- The Significance of the Cell-Mediated Host Immune Response in Syphilis.Microorganisms · 2024Review
- Immunoinhibitory effects of anti-tuberculosis therapy induce the host vulnerability to tuberculosis recurrence.Microbiology spectrum · 2024Article
- Recognition of Mycobacterium tuberculosis by macrophage Toll-like receptor and its role in autophagy.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2024Review
- The role of ESAT-6 in tuberculosis immunopathology.Frontiers in immunology · 2024Review
- ESAT-6 protein suppresses allograft rejection by inducing CD4Frontiers in immunology · 2024Article
- Role of pattern recognition receptors in sensingHeliyon · 2023Review
- Biapenem, a Carbapenem Antibiotic, Elicits Mycobacteria Specific Immune Responses and Reduces the Recurrence of Tuberculosis.Microbiology spectrum · 2023Article
- Berberine governs NOTCH3/AKT signaling to enrich lung-resident memory T cells during tuberculosis.PLoS pathogens · 2023Article
- Identification of a Potential Vaccine againstVaccines · 2022Article
- Vaccination Strategies Based on Bacterial Self-Assembling Proteins as Antigen Delivery Nanoscaffolds.Vaccines · 2022Review
- Expression and epitope prediction of MPT64 recombinant proteins from clinical isolates ofVeterinary world · 2022Article
- Protein-Based Adjuvants for Vaccines as Immunomodulators of the Innate and Adaptive Immune Response: Current Knowledge, Challenges, and Future Opportunities.Pharmaceutics · 2022Review
- The 1, 2-ethylenediamine SQ109 protects against tuberculosis by promoting M1 macrophage polarization through the p38 MAPK pathway.Communications biology · 2022Article
- Interaction of Mycobacteria With Host Cell Inflammasomes.Frontiers in immunology · 2022Review
- A century of BCG vaccination: Immune mechanisms, animal models, non-traditional routes and implications for COVID-19.Frontiers in immunology · 2022Review
- Article
- Luteolin as a potential host-directed immunotherapy adjunct to isoniazid treatment of tuberculosis.PLoS pathogens · 2021Article
- Article
35 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 4 countries.
Funding
Abstract
Despite its relatively poor efficacy, Bacillus Calmette-Guérin (BCG) has been used as a tuberculosis (TB) vaccine since its development in 1921. BCG induces robust T helper 1 (Th1) immune responses but, for many individuals, this is not sufficient for host resistance against Mycobacterium tuberculosis (M. tb) infection. Here we provide evidence that early secreted antigenic target protein 6 (ESAT-6), expressed by the virulent M. tb strain H37Rv but not by BCG, promotes vaccine-enhancing Th17 cell responses. These activities of ESAT-6 were dependent on TLR-2/MyD88 signalling and involved IL-6 and TGF-β production by dendritic cells. Thus, animals that were previously infected with H37Rv or recombinant BCG containing the RD1 region (BCG::RD1) exhibited improved protection upon re-challenge with virulent H37Rv compared with mice previously infected with BCG or RD1-deficient H37Rv (H37RvΔRD1). However, TLR-2 knockout (TLR-2⁻/⁻) animals neither showed Th17 responses nor exhibited improved protection in response to immunization with H37Rv. Furthermore, H37Rv and BCG::RD1 infection had little effect on the expression of the anti-inflammatory microRNA-146a (miR146a) in dendritic cells (DCs), whereas BCG and H37RvΔRD1 profoundly induced its expression in DCs. Consistent with these findings, ESAT-6 had no effect on miR146a expression in uninfected DCs, but dramatically inhibited its upregulation in BCG-infected or LPS-treated DCs. Collectively, our findings indicate that, in addition to Th1 immunity induced by BCG, RD1/ESAT-6-induced Th17 immune responses are essential for optimal vaccine efficacy.
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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.