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The value of transcriptomics in advancing knowledge of the immune response and diagnosis in tuberculosis

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Abstract

Blood transcriptomics analysis of tuberculosis has revealed an interferon-inducible gene signature that diminishes in expression after successful treatment; this promises improved diagnostics and treatment monitoring, which are essential for the eradication of tuberculosis. Sensitive radiography revealing lung abnormalities and blood transcriptomics have demonstrated heterogeneity in patients with active tuberculosis and exposed asymptomatic people with latent tuberculosis, suggestive of a continuum of infection and immune states. Here we describe the immune response to infection with Mycobacterium tuberculosis revealed through the use of transcriptomics, as well as differences among clinical phenotypes of infection that might provide information on temporal changes in host immunity associated with evolving infection. We also review the diverse blood transcriptional signatures, composed of small sets of genes, that have been proposed for the diagnosis of tuberculosis and the identification of at-risk asymptomatic people and suggest novel approaches for the development of such biomarkers for clinical use.

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Fig. 1: Heterogeneity of outcomes after exposure to M. tuberculosis.
Fig. 2: The immune response to M. tuberculosis infection.
Fig. 3: Modular host gene signatures in tuberculosis and in other infections and diseases.

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Acknowledgements

A.S., R.J.W. and A.O.G. were funded by The Francis Crick Institute (Crick 10126 and Crick 10468 for A.O.G. and A.S., and Crick 10128 for R.J.W.), which receives its core funding from Cancer Research UK, the UK Medical Research Council and the Wellcome Trust. R.J.W. was supported by the Wellcome Trust (104803 and 203135); MRC South Africa under strategic health innovation partnerships EDCTP SR1A 2015-1065 and the US National Institutes of Health (019 AI 111276 and UO1AI115940). P.H. was supported by NIHR Leicester Biomedical Research Centre and the University of Leicester. M.R. was supported by Medical Diagnostic Discovery Department, bioMérieux SA, Marcy l’Etoile, France. The views expressed are those of the author(s) and not necessarily those of the NHS the NIHR or the Department of Health.

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Authors and Affiliations

  1. Laboratory of Immunoregulation and Infection, The Francis Crick Institute, London, UK

    Akul Singhania & Anne O’Garra

  2. Laboratory of Tuberculosis, The Francis Crick Institute, London, UK

    Robert J. Wilkinson

  3. Department of Medicine, Imperial College London, London, UK

    Robert J. Wilkinson

  4. Wellcome Centre for Infectious Diseases Research in Africa, University of Cape Town, Observatory, 7925, Cape Town, Republic of South Africa

    Robert J. Wilkinson

  5. Medical Diagnostic Discovery Department, bioMerieux SA, Marcy l’Etoile, France

    Marc Rodrigue

  6. Respiratory Biomedical Research Centre, Institute for Lung Health, Department of Infection Immunity and Inflammation, University of Leicester, Leicester, UK

    Pranabashis Haldar

  7. National Heart and Lung Institute, Imperial College London, London, UK

    Anne O’Garra

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Correspondence to Anne O’Garra.

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The authors declare no competing interests. Patents previously held by A.O.G. on the use of the blood transcriptome for the diagnosis of tuberculosis have lapsed and have been discontinued. M.R. is an employee of BioMérieux, which has not filed patents related to this study.

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Singhania, A., Wilkinson, R.J., Rodrigue, M. et al. The value of transcriptomics in advancing knowledge of the immune response and diagnosis in tuberculosis. Nat Immunol 19, 1159–1168 (2018). https://doi.org/10.1038/s41590-018-0225-9

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