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

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-alpha and interleukin 1 beta, 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.