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

Frontiers in Microbiology

Naomi F. Walker²  Robert J. Wilkinson⁴  Cari Stek⁵  Brian Allwood⁶  Lutgarde Lynen⁷  Graeme Meintjes⁸ 

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

关键词: tuberculosis;    lung damage;    host-directed therapy;    cavity;    pulmonary function;    matrix metalloproteinase;   

DOI  :  10.3389/fmicb.2018.02603

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown