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Front Microbiol. 2018 Oct 30;9:2603. doi: 10.3389/fmicb.2018.02603. eCollection 2018.

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

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Wellcome Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa.
Department of Clinical Sciences, Institute of Tropical Medicine Antwerp, Antwerp, Belgium.
Department of Medicine, University of Cape Town, Cape Town, South Africa.
Division of Pulmonology, Department of Medicine, Stellenbosch University, Stellenbosch, South Africa.
Department of Clinical Research, London School of Hygiene & Tropical Medicine, London, United Kingdom.
Department of Medicine, Imperial College London, London, United Kingdom.
Francis Crick Institute, London, United Kingdom.


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.


cavity; host-directed therapy; immune mechanisms; lung damage; matrix metalloproteinase; neutrophils; pulmonary function; tuberculosis

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