Tuberculosis (TB) is an airborne disease caused by Mycobacterium tuberculosis (Mtb) that often affects the lungs with clinical manifestation of chronic cough, fever, persistent weight loss, emaciation, and hemoptysis (ie, hemoptysis or bloody mucus) [1]. Mtb is a non-motile, aerobic, rod-shaped bacterium that spread almost exclusively by droplet infection. Frequency, duration and distance of exposure to patients with infectious pulmonary TB, number and virulence of pathogens as well as the susceptibility of exposed individuals play a decisive role in Mtb infection [2]. TB remains a global health problem. According to the Global Tuberculosis Report 2021 released by the World Health Organization, the mortality rate of TB is rising in most countries, particularly among the male population [3]. Based on findings in previous studies that lung injury severity is associated with neutrophil abundance and activity in TB, this study aimed to undertake further research. Neutrophils are the predominant cell types infected with Mtb in the sputum, bronchoalveolar lavage fluid (BAL) and cavity of patients with TB [4]. However, the exact role of neutrophils in the pathogenesis of TB is poorly understood. In some studies, neutrophils are considered key mediators of innate TB immunopathology that prevent mycobacterial invasion. Following mycobacterial activation, neutrophils perform several specialized functions, including chemotaxis, phagocytosis, production of reactive oxygen species metabolites, and activation of other immune cells [5]. A study of close contacts of patients with pulmonary TB showed that peripheral blood neutrophil counts were negatively correlated with the risk of Mtb infection [6]. Besides, the boosting growth of Mtb with the depletion of neutrophils from whole blood in vitro [7] suggests that neutrophils can play an active role in limiting infection. Another study found that neutrophils trigger a high inflammatory response leading to tissue destruction and mediate injury and lung disease during active TB [8,9]. Neutrophils are not only independently associated with an increased risk of cavitation and lung tissue damage in patients treated for TB [10] but also associated with the mortality rate [11].

This study performed weighted gene co-expression network analysis (WGCNA) of neutrophil-related genes in TB samples from the GEO database and identified module genes. After constructing a random forest classification model for key module genes, the top 10 genes in the model were subjected to differential expression analysis. Finally, immune microenvironment analysis and HLA differential expression analysis were conducted for different sample subtypes obtained by K-means clustering analysis. In conclusion, our study shed new light on the role of neutrophils in TB.