Blood transcriptomics reveal the evolution and resolution of the immune response in tuberculosis

Author:

Tabone Olivier1ORCID,Verma Raman2ORCID,Singhania Akul1ORCID,Chakravarty Probir3ORCID,Branchett William J.1ORCID,Graham Christine M.1ORCID,Lee Jo2ORCID,Trang Tran4ORCID,Reynier Frederic4ORCID,Leissner Philippe4ORCID,Kaiser Karine5ORCID,Rodrigue Marc6ORCID,Woltmann Gerrit2ORCID,Haldar Pranabashis2,O’Garra Anne17ORCID

Affiliation:

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

2. Department of Respiratory Sciences, National Institute for Health Research Respiratory Biomedical Research Centre, University of Leicester, UK

3. Bioinformatics Core, The Francis Crick Institute, London, UK

4. Bioaster Microbiology Technology Institute, Lyon, France

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

6. Global Medical Affairs, bioMérieux SA, Marcy l’Etoile, France

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

Abstract

Blood transcriptomics have revealed major characteristics of the immune response in active TB, but the signature early after infection is unknown. In a unique clinically and temporally well-defined cohort of household contacts of active TB patients that progressed to TB, we define minimal changes in gene expression in incipient TB increasing in subclinical and clinical TB. While increasing with time, changes in gene expression were highest at 30 d before diagnosis, with heterogeneity in the response in household TB contacts and in a published cohort of TB progressors as they progressed to TB, at a bulk cohort level and in individual progressors. Blood signatures from patients before and during anti-TB treatment robustly monitored the treatment response distinguishing early and late responders. Blood transcriptomics thus reveal the evolution and resolution of the immune response in TB, which may help in clinical management of the disease.

Funder

Francis Crick Institute

Cancer Research UK

UK Medical Research Council

Wellcome Trust

BIOASTER Microbiology Technology Institute

French Government Investissement d’Avenir

bioMérieux SA

National Institute for Health Research Leicester Biomedical Research Centre

University of Leicester

Wellcome Investigator Award

Publisher

Rockefeller University Press

Subject

Immunology,Immunology and Allergy

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