ArticleThe Journal of clinical investigation2016
ESAT-6-dependent cytosolic pattern recognition drives noncognate tuberculosis control in vivo.
Article in The Journal of clinical investigation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
39 citing papers in PubMed, 1 synthesis or guideline pooled it, 62 citations in OpenAlex.
- Systematic review of innate immune responses againstFrontiers in immunology · 2024Pooled it
- Bacillus Calmette-Guérin (BCG) Revaccination of Adults with Latent Mycobacterium tuberculosis Infection Induces Long-Lived BCG-Reactive NK Cell Responses.Journal of immunology (Baltimore, Md. : 1950) · 2016Trial
- VEGFR Blockade ReducesCells · 2026Article
- CD8Nature communications · 2026Article
- Alpha-galactosylceramide as mRNA vaccine adjuvant modulates cellular immunity against tuberculosis and contributes to antigen-specific lung-associated T cells with a TRM-associated phenotype following prime-pull strategy.Frontiers in immunology · 2026Article
- Functional analysis of type VII secretion system links to host immune evasion mechanism inFrontiers in cellular and infection microbiology · 2026Review
- Cytotoxic granules and effector molecules from immune cells in tuberculosis: Mechanisms of host defense and therapeutic potential.Virulence · 2025Review
- Article
- Recent Developments in Mycobacteria-Based Live Attenuated Vaccine Candidates for Tuberculosis.Biomedicines · 2022Review
- Recombinant BCGs for tuberculosis and bladder cancer.Vaccine · 2021Review
- Article
- Mucosal delivery of ESX-1-expressing BCG strains provides superior immunity against tuberculosis in murine type 2 diabetes.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Treatment of mice with S4B6 IL-2 complex prevents lethal toxoplasmosis via IL-12- and IL-18-dependent interferon-gamma production by non-CD4 immune cells.Scientific reports · 2020Article
- Host defense mechanisms against Mycobacterium tuberculosis.Cellular and molecular life sciences : CMLS · 2020Review
- A systematic approach to simultaneously evaluate safety, immunogenicity, and efficacy of novel tuberculosis vaccination strategies.Science advances · 2020Article
- Vaccines Against Tuberculosis: Problems and Prospects (Review).Applied biochemistry and microbiology · 2020Article
- A SNP upstream of the cyclic GMP-AMP synthase (cGAS) gene protects from relapse and extra-pulmonary TB and relates to BCG vaccination status in an Indian cohort.Genes and immunity · 2020Article
- Targeting Unconventional Host Components for Vaccination-Induced Protection Against TB.Frontiers in immunology · 2020Review
- Tuberculosis Vaccine Development: Progress in Clinical Evaluation.Clinical microbiology reviews · 2019Review
- ESX/Type VII Secretion Systems-An Important Way Out for Mycobacterial Proteins.Microbiology spectrum · 2019Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
IFN-γ is a critical mediator of host defense against Mycobacterium tuberculosis (Mtb) infection. Antigen-specific CD4+ T cells have long been regarded as the main producer of IFN-γ in tuberculosis (TB), and CD4+ T cell immunity is the main target of current TB vaccine candidates. However, given the recent failures of such a TB vaccine candidate in clinical trials, strategies to harness CD4-independent mechanisms of protection should be included in future vaccine design. Here, we have reported that noncognate IFN-γ production by Mtb antigen-independent memory CD8+ T cells and NK cells is protective during Mtb infection and evaluated the mechanistic regulation of IFN-γ production by these cells in vivo. Transfer of arenavirus- or protein-specific CD8+ T cells or NK cells reduced the mortality and morbidity rates of mice highly susceptible to TB in an IFN-γ-dependent manner. Secretion of IFN-γ by these cell populations required IL-18, sensing of mycobacterial viability, Mtb protein 6-kDa early secretory antigenic target-mediated (ESAT-6-mediated) cytosolic contact, and activation of NLR family pyrin domain-containing protein 3 (NLRP3) inflammasomes in CD11c+ cell subsets. Neutralization of IL-18 abrogated protection in susceptible recipient mice that had received noncognate cells. Moreover, improved Mycobacterium bovis bacillus Calmette-Guérin (BCG) vaccine-induced protection was lost in the absence of ESAT-6-dependent cytosolic contact. Our findings provide a comprehensive mechanistic framework for antigen-independent IFN-γ secretion in response to Mtb with critical implications for future intervention strategies against TB.
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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.