The role of neutrophil response in lung damage and post-tuberculosis lung disease: a translational narrative review

It is estimated that more than 150 million individuals alive in 2020 had survived tuberculosis (TB). A portion of this large population continues to experience chronic respiratory abnormalities, with or without symptoms, due to previous active pulmonary TB. This condition known as Post-TB Lung Disease (PTLD), involves a complex interaction between pathogen, host and environmental factors. These interactions are believed to drive a hyperinflammatory process in the lungs during active TB, resulting in tissue damage, which may lead to radiological sequelae, impaired pulmonary function, clinical symptoms, such as cough, dyspnea, hemoptysis, and respiratory infections. Such complications impose significant health, financial, and social burdens, which remain poorly understood and inadequately addressed by health care systems. Given the heterogeneity of immune cells and their products infiltrating the airways and the lung parenchyma during acute and chronic inflammation caused by Mycobacterium tuberculosis infection, it is evident that TB immunopathology is multifactorial. Among the various components involved, neutrophils have recently emerged as critical contributors to the deleterious immune response against TB, leading to severe pulmonary damage. In this translational narrative review, we aim to summarize the role of neutrophils and their primary products - proteases (such as elastase), matrix metalloproteinases and neutrophils extracellular traps (NETs) - in pulmonary TB. We highlight new concepts and emerging evidence of neutrophil involvement during the active disease, translating these insights from "bench to bedside" to facilitate dialogue between fundamental researchers and clinical practitioners. Additionally, we present potential targets for future treatment strategies that could mitigate or even prevent PTLD.