An interferon-inducible neutrophil-driven blood transcriptional signature in human tuberculosis
Open accessAbstract
Tuberculosis (TB), caused by infection with Mycobacterium tuberculosis, is a major cause of morbidity and mortality worldwide. Efforts to control it are hampered by difficulties with diagnosis, prevention and treatment. Most people infected with M. tuberculosis remain asymptomatic, termed latent TB, with a 10% lifetime risk of developing active TB disease. Current tests, however, cannot identify which individuals will develop disease. The immune response to M. tuberculosis is complex and incompletely characterized, hindering development of new diagnostics, therapies and vaccines. Here we identify a whole-blood 393 transcript signature for active TB in intermediate and high-burden settings, correlating with radiological extent of disease and reverting to that of healthy controls after treatment. A subset of patients with latent TB had signatures similar to those in patients with active TB. We also identify a specific 86-transcript signature that discriminates active TB from other inflammatory and infectious diseases. Modular and pathway analysis revealed that the TB signature was dominated by a neutrophil-driven interferon (IFN)-inducible gene profile, consisting of both IFN-gamma and type I IFN-alphabeta signalling. Comparison with transcriptional signatures in purified cells and flow cytometric analysis suggest that this TB signature reflects changes in cellular composition and altered gene expression. Although an IFN-inducible signature was also observed in whole blood of patients with systemic lupus erythematosus (SLE), their complete modular signature differed from TB, with increased abundance of plasma cell transcripts. Our studies demonstrate a hitherto underappreciated role of type I IFN-alphabeta signalling in the pathogenesis of TB, which has implications for vaccine and therapeutic development. Our study also provides a broad range of transcriptional biomarkers with potential as diagnostic and prognostic tools to combat the TB epidemic.
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IFN-β transcriptome signatures are associated with active but not latent TB.
“Therefore, it is no surprise that IFN-β transcriptome signatures were found to be associated with active but not latent TB (101).”
From Macrophage defense mechanisms against intracellular bacteria (2015) · cites this paper as [101]
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- Authors
- Berry, M. P. R., Graham, C. M., McNab, F. W., Xu, Z., Bloch, S. A. A., Oni, T., Wilkinson, K. A., Banchereau, R., Skinner, J., Wilkinson, R. J., Quinn, C., Blankenship, D., Dhawan, R., Cush, J. J., Mejias, A., Ramilo, O., Kon, O. M., Pascual, V., Banchereau, J., Chaussabel, D., & O’Garra, A.
- Affiliations
- National Institute for Medical Research (GB)
- Inserm (FR)
- Imperial College Healthcare NHS Trust (GB)
- University of Cape Town (ZA)
- The University of Texas Southwestern Medical Center (US)
- Baylor Scott & White Health (US)
- Nationwide Children's Hospital (US)
- Corresponding author
- O’Garra, Anne
- ORCID
- Venue
- Nature
- Published
- 2010-08
- Volume
- 466
- Issue
- 7309
- Pages
- 973-977
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC3492754
- OpenAlex
- W2109543073
- Cited by
- 1,898
- References
- 29
- Citations by year
- 2026: 104 · 2025: 105 · 2024: 112 · 2023: 108 · 2022: 99 · 2021: 121 · 2020: 113 · 2019: 127 · 2018: 137 · 2017: 134 · 2016: 149 · 2015: 126 · 2014: 119 · 2013: 127 · 2012: 114
- FWCI
- 70.93
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- Wellcome Trust (088316, 84323)
- Imperial College Healthcare NHS Trust
- U.S. Public Health Service (U19 AIO57234-02, P50 ARO54083)
- Medical Research Council
- National Cancer Institute (P01CA084512)
- National Institute of Allergy and Infectious Diseases (U19AI057234, U01AI082110, U19AI082715)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR050770, P50AR054083)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Tuberculosis Research and Epidemiology
- Health Sciences › Medicine › Surgery › Infectious Diseases and Tuberculosis
- Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Keywords
- tuberculosis, Mycobacterium tuberculosis, latent tuberculosis infection, active tuberculosis, whole blood transcriptome, interferon-stimulated genes, neutrophils, interferon-gamma signaling, type I interferon, transcriptomic biomarkers, diagnostic biomarkers, prognostic factors, systemic lupus erythematosus, cell composition, treatment response monitoring
- MeSH terms
- Blood, Gene Expression Regulation, Humans, Interferon Type I, Lupus Erythematosus, Systemic, Mycobacterium tuberculosis, Neutrophils, Transcription, Genetic, Tuberculosis, Tuberculosis, Pulmonary, Signal Transduction, Case-Control Studies, Gene Expression Profiling, Latent Tuberculosis
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