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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
general
An interferon-inducible neutrophil-driven blood transcriptional signature in human tuberculosis
Nature, Volume 466, No. 7309, Year 2010
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Description
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-γ and type I IFN-αβ 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-αβ 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. © 2010 Macmillan Publishers Limited. All rights reserved.
Authors & Co-Authors
Berry, Matthew P.R.
United Kingdom, London
Mrc National Institute for Medical Research
Graham, Christine Marian
United Kingdom, London
Mrc National Institute for Medical Research
Mcnab, Finlay W.
United Kingdom, London
Mrc National Institute for Medical Research
Xu, Zhaohui
United States, Dallas
Baylor Institute for Immunology Research
Bloch, Susannah A.A.
United Kingdom, London
Imperial College Healthcare Nhs Trust
Oni, Tolu
South Africa, Cape Town
University of Cape Town
United Kingdom, London
Imperial College London
Andrea Wilkinson, Katalin Andrea
United Kingdom, London
Mrc National Institute for Medical Research
South Africa, Cape Town
University of Cape Town
Banchereau, Romain
United States, Dallas
Ut Southwestern Medical Center
Skinner, Jason
United States, Dallas
Baylor Institute for Immunology Research
Wilkinson, Robert J.
United Kingdom, London
Mrc National Institute for Medical Research
South Africa, Cape Town
University of Cape Town
United Kingdom, London
Imperial College London
Quinn, Charles
United States, Dallas
Baylor Institute for Immunology Research
Blankenship, Derek
United States
Baylor Health Care System
Dhawan, Ranju
United Kingdom, London
Imperial College Healthcare Nhs Trust
Cush, John J.
United States, Dallas
Baylor Institute for Immunology Research
Mejías, Asunciõn
United States, Columbus
Research Institute at Nationwide Childrens Hospital
Ramilo, Octavio
United States, Columbus
Research Institute at Nationwide Childrens Hospital
Kon, Onn Min
United Kingdom, London
Imperial College Healthcare Nhs Trust
Pascual, Virginia
United States, Dallas
Baylor Institute for Immunology Research
Banchereau, Jacques F.J.
United States, Dallas
Baylor Institute for Immunology Research
Chaussabel, Damien
United States, Dallas
Baylor Institute for Immunology Research
O’Garra, Anne
United Kingdom, London
Mrc National Institute for Medical Research
Statistics
Citations: 1,593
Authors: 21
Affiliations: 8
Identifiers
Doi:
10.1038/nature09247
ISSN:
00280836
e-ISSN:
14764687
Research Areas
Genetics And Genomics
Infectious Diseases