Different macrophage polarization between drug-susceptible and multidrug-resistant pulmonary tuberculosis

Hyun Jin Cho,Chang-Hwa Song,Won-Jung Koh,Jhingook Kim,Yun-Ji Lim,Min-Woong Kang

doi:10.1186/s12879-020-4802-9

Abstract

BackgroundMacrophages play a key role in the infection process, and alternatively activated macrophages (M2 polarization) play important roles in persistent infection via the immune escape of pathogens. This suggests that immune escape of pathogens from host immunity is an important factor to consider in treatment failure and multidrug-resistant tuberculosis (MDR-TB)/extensively drug-resistant tuberculosis (XDR-TB). In this study, we investigated the association between macrophage polarization and MDR-TB/XDR-TB and the association between macrophage polarization and the anti-TB drugs used.MethodsiNOS and arginase-1, a surface marker of polarized macrophages, were quantified by immunohistochemical staining and imaging analysis of lung tissues of patients who underwent surgical treatment for pulmonary TB. Drug susceptibility/resistance and the type and timing of anti-tuberculosis drugs used were investigated.ResultsThe M2-like polarization rate and the ratio of the M2-like polarization rate to the M1-like polarization rate were significantly higher in the MDR-TB/XDR-TB group than in the DS-TB group. The association between a high M2-like polarization rate and MDR-TB/XDR-TB was more pronounced in patients with a low M1-like polarization rate. Younger age and a higher M2-like polarization rate were independent associated factors for MDR-TB/XDR-TB. The M2-like polarization rate was significantly higher in patients who received anti-TB drugs containing pyrazinamide continuously for 4 or 6 weeks than in those who received anti-TB drugs not containing pyrazinamide.ConclusionsThe M2-like polarization of macrophages is associated with MDR-TB/XDR-TB and anti-TB drug regimens including pyrazinamide or a combination of pyrazinamide, prothionamide and cycloserine.

Highlights

Macrophages play a key role in the infection process, and alternatively activated macrophages (M2 polarization) play important roles in persistent infection via the immune escape of pathogens
Alternatively activated macrophages (M2 polarization) play important roles in tissue repair, tumor progression, and persistent infection via the immune escape of tumors and pathogens [4, 9, 10]. This suggests that immune escape of pathogens from the host immunity is an important factor to consider in treatment failure and multidrug-resistant tuberculosis (MDR-TB)/Extensively drugresistant tuberculosis (XDR-TB)
This study investigated the dominant macrophage polarization in tuberculous granulomas obtained from surgically resected lung specimens of MDRTB/XDR-TB and drug-susceptible TB (DS-TB) patients, and analyzed which anti-TB drugs are correlated with the M2-like polarized environment in MDR-TB/XDRTB patients

Summary

Introduction

Macrophages play a key role in the infection process, and alternatively activated macrophages (M2 polarization) play important roles in persistent infection via the immune escape of pathogens This suggests that immune escape of pathogens from host immunity is an important factor to consider in treatment failure and multidrug-resistant tuberculosis (MDR-TB)/extensively drug-resistant tuberculosis (XDR-TB). Alternatively activated macrophages (M2 polarization) play important roles in tissue repair, tumor progression, and persistent infection via the immune escape of tumors and pathogens [4, 9, 10] This suggests that immune escape of pathogens from the host immunity is an important factor to consider in treatment failure and MDR-TB/XDR-TB. We found that alternatively activated macrophages were more abundant in the lung tissue of MDR-TB patients than in the lung tissue of new-onset TB patients, the sample size was small [11]

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