Triggering Receptor Expressed on Myeloid Cells 2 Mediates the Involvement of M2-Type Macrophages in Pulmonary Tuberculosis Infection

Abstract

Xiaoqian Shang,1,* Naifeisha Maimaiti,1,* Jiahui Fan,1 Liang Wang,2 Yuanyuan Wang,3 Hu Sun,3 Jie Lv,1 Xiufeng Zhang,4 Jing Wang,4 Xiumin Ma1 1State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Clinical Laboratory Center, Tumor Hospital Affiliated to Xinjiang Medical University, Urumqi, Xinjiang, 830011, People’s Republic of China; 2The Fifth Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, 830011, People’s Republic of China; 3First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, 830011, People’s Republic of China; 4Department of Respiratory Medicine, Second Affiliated Hospital of Hainan Medical University, Haikou, Hainan, 570100, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiumin Ma, State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Clinical Laboratory Center, Tumor Hospital Affiliated to Xinjiang Medical University, Urumqi, Xinjiang, 830011, People’s Republic of China, Email [email protected] Jing Wang, Department of Respiratory Medicine, Second Affiliated Hospital of Hainan Medical University, Haikou, Hainan, 570100, People’s Republic of China, Email [email protected]: Macrophage play a significant work in the development of tuberculosis. This study aims to investigate the relationship between TREM2 and macrophage polarization, as well as the related cytokines.Methods: This study involved 43 pulmonary tuberculosis patients and 37 healthy controls. Enzyme-linked immunosorbent assay (ELISA) was used to detect the expression levels of M1/M2 macrophage-related cytokines IL-10 and IL-12 in the peripheral blood of pulmonary tuberculosis patients. The relative mRNA expression levels of TREM2, IL-10 and IL-12 were detected using quantitative real-time PCR (qRT-PCR). Additionally, Spearman rank correlation analysis was used to preliminarily assess the correlation between TREM2 and M1 / M2 macrophages. Hematoxylin-eosin (HE) staining was performed to observe the pathological manifestations of pulmonary tuberculosis lesions. Immunohistochemical (IHC) staining was used to observe the localization of the macrophage-specific molecule CD68, the M1 specific molecule iNOS, the M2 specific molecule CD163, and TREM2.Results: The lesions of pulmonary tuberculosis patients showed Langhans multinucleated macrophages and tuberculous granulomas. The ELISA results indicated that the expression levels of IL-10 and IL-12 were significantly increased in peripheral blood of pulmonary tuberculosis patients. Additionally, the relative mRNA expression levels of TREM2, IL-10 and IL-12 were also significantly higher in the pulmonary tuberculosis group. Furthermore, a positive correlation was observed between TREM2 and IL-10, which are secreted by M2 macrophages. IHC revealed significant positivity of TREM2 and macrophage-related markers in tuberculous granuloma. Specifically, TREM2 and M2 macrophage marker CD163 were significantly expressed in the cytoplasm and membrane of Langhans multinucleated macrophages.Conclusion: The role of macrophage polarization in pulmonary tuberculosis is significant, and further investigation is needed to understand relationship between TREM2 and M2 macrophages.Keywords: tuberculosis, TREM2, macrophage

Keywords

• tuberculosis
• trem2
• macrophage