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Int J Infect Dis. 2019 Mar;80S:S58-S61. doi: 10.1016/j.ijid.2019.02.035. Epub 2019 Feb 26.

Latent TB Infection (LTBI) - Mycobacterium tuberculosis pathogenesis and the dynamics of the granuloma battleground.

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Champalimaud Centre for the Unknown, Lisbon, Portugal. Electronic address:
National Institute for Infectious Diseases, Lazzaro Spallanzani, Rome, Italy. Electronic address:
National Institute of Medical Research Muhimbili, Dar es Salaam, Tanzania. Electronic address:
University Marien NGouabi and Fondation Congolaise pour la Recherche Médicale (FCRM), Brazzaville, Congo; Institute for Tropical Medicine, University of Tübingen, Germany. Electronic address:
Department of Bacteriology, Noguchi Memorial Institute for Medical Research, Accra, Ghana. Electronic address:
Experimental Tuberculosis Unit (UTE), Fundació Institut Germans Trias i Pujol (IGTP), Universitat Autònoma de Barcelona (UAB), Badalona, Catalonia, Spain. Electronic address:
Division of Infection and Immunity, University College London and NIHR Biomedical Research Centre, UCL Hospitals NHS Foundation Trust, London, UK. Electronic address:
Champalimaud Centre for the Unknown, Avenida Brasília, 1400-038 Lisbon, Portugal; Department of Haematology and Oncology, Krankenhaus Nordwest, Frankfurt, Germany. Electronic address:


Latent tuberculosis infection (LTBI) is established in over 90% of persons infected with Mycobacterium tuberculosis (Mtb), from whom new active TB cases will arise. Understanding the spatio-temporal dynamics of host immune responses in LTBI granulomas is essential to designing effective post-exposure therapies that inhibit progression to TB. Information arising from cancer studies and other modalities - where local chronic inflammation leads to immunopathology - can help provide insights into the biological pathways at play in LTBI granulomas. Translational studies using patient material as well as LTBI+ donor-derived tissue samples are instrumental in understanding the various components of granuloma dynamics, immunological landscapes therein and how this could help to identify therapeutic targets. Deep sequencing technologies may aid to decipher the genetic changes in lung granuloma and blood samples from LTBI+ individuals associated with progression to active TB disease. This may lead to advancement of development of targeted Host-Directed Therapies (HDTs) and their evaluation as adjunct TB therapies for improving treatment outcomes for LTBI and pulmonary TB.


granuloma; host-directed therapies; immune landscape; latent tuberculosis infection; mutations

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