4.7 Article

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

期刊

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ELSEVIER SCI LTD
DOI: 10.1016/j.ijid.2019.02.035

关键词

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

资金

  1. European and Developing Countries Clinical Trials Partnership (EDCTP2) programme [RIA2016E-1609]
  2. Italian Ministry of Health [4]
  3. Champalimaud Foundation

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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. (c) 2019 Published by Elsevier Ltd on behalf of International Society for Infectious Diseases. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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