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The Immune Mechanisms of Lung Parenchymal Damage in Tuberculosis and the Role of Host-Directed Therapy

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Title: The Immune Mechanisms of Lung Parenchymal Damage in Tuberculosis and the Role of Host-Directed Therapy
Authors: Stek, C
Allwood, B
Walker, NF
Wilkinson, RJ
Lynen, L
Meintjes, G
Item Type: Journal Article
Abstract: Impaired lung function is common in people with a history of tuberculosis. Host-directed therapy added to tuberculosis treatment may reduce lung damage and result in improved lung function. An understanding of the pathogenesis of pulmonary damage in TB is fundamental to successfully predicting which interventions could be beneficial. In this review, we describe the different features of TB immunopathology that lead to impaired lung function, namely cavities, bronchiectasis, and fibrosis. We discuss the immunological processes that cause lung damage, focusing on studies performed in humans, and using chest radiograph abnormalities as a marker for pulmonary damage. We highlight the roles of matrix metalloproteinases, neutrophils, eicosanoids and cytokines, like tumor necrosis factor-α and interleukin 1β, as well as the role of HIV co-infection. Finally, we focus on various existing drugs that affect one or more of the immunological mediators of lung damage and could therefore play a role as host-directed therapy.
Issue Date: 30-Oct-2018
Date of Acceptance: 11-Oct-2018
URI: http://hdl.handle.net/10044/1/64382
DOI: https://dx.doi.org/10.3389/fmicb.2018.02603
ISSN: 1664-302X
Publisher: FRONTIERS MEDIA SA
Journal / Book Title: FRONTIERS IN MICROBIOLOGY
Volume: 9
Copyright Statement: © 2018 Stek, Allwood, Walker, Wilkinson, Lynen and Meintjes. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY https://creativecommons.org/licenses/by/4.0/). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Sponsor/Funder: Wellcome Trust
Funder's Grant Number: 104803/Z/14/ZR
Keywords: Science & Technology
Life Sciences & Biomedicine
Microbiology
tuberculosis
lung damage
host-directed therapy
cavity
pulmonary function
matrix metalloproteinase
neutrophils
immune mechanisms
RECONSTITUTION INFLAMMATORY SYNDROME
TUMOR-NECROSIS-FACTOR
ACTIVE PULMONARY TUBERCULOSIS
HIV-ASSOCIATED TUBERCULOSIS
NON-CAVITARY TUBERCULOSIS
MYCOBACTERIUM-TUBERCULOSIS
MATRIX METALLOPROTEINASES
INTERFERON-GAMMA
FACTOR-ALPHA
ANTIRETROVIRAL THERAPY
Publication Status: Published
Open Access location: https://www.frontiersin.org/articles/10.3389/fmicb.2018.02603/full
Article Number: ARTN 2603
Online Publication Date: 2018-10-30
Appears in Collections:Department of Medicine



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