Temporal upregulation of TREM2 parallel to M2 macrophage marker expression in tuberculosis: implications for macrophage polarization regulation.

BACKGROUND

This study aims to explore the association between Triggering Receptor Expressed on Myeloid Cells 2 (TREM2) expression and tuberculosis pathogenesis, with particular focus on its potential correlation with established macrophage polarization markers.

METHODS

The inflammatory pathology of lung tissues in mock-infected mice was evaluated using hematoxylin and eosin (H&E) staining. Additionally, the expression and localization of M1/M2 macrophage-specific markers and TREM2 were assessed via immunohistochemical (IHC) staining. The expression levels and localization of M1/M2 macrophage-associated cytokines, including IL-10 and IL-6, were measured in peripheral blood using enzyme-linked immunosorbent assay (ELISA) and quantitative real-time PCR (qRT-PCR). Mycobacterium smegmatis suspensions were co-cultured with THP-1-derived macrophages and RAW264.7 macrophages. Temporal changes in the expression of TREM2 and M1/M2 macrophage-specific markers were analyzed at different time points using qRT-PCR and Western blot.

RESULTS

I In the experimental group of mice, lung lesions exhibited widened alveolar septa, interstitial edema, and extensive infiltration of inflammatory cells and erythrocytes. TREM2 and inflammatory markers (iNOS and IL-10) showed significant positive expression in the infected lung tissues. Compared to the control group, the Mycobacterium-infected mouse model displayed significantly higher mRNA expression levels of TREM2, along with increased IL-10 and IL-6 production. Following co-culture with Mycobacterium smegmatis, both THP-1-derived macrophages and RAW264.7 cells exhibited upregulated TREM2 mRNA and protein expression. This upregulation was more closely associated with M2-type macrophage markers than with M1-type markers. Preferential TREM2 expression in M2 macrophages post-infection Notably, after Mycobacterium smegmatis infection, TREM2 expression was significantly more pronounced in M2-polarized macrophages compared to their M1 counterparts.

CONCLUSION

TREM2 expression was significantly upregulated in lung tissues of tuberculosis-infected murine models, correlating strongly with increased expression of macrophage-derived cytokines. Notably, in vitro infection studies revealed that TREM2 upregulation followed a temporal pattern parallel to M2 macrophage marker expression. These findings suggest that TREM2 may be associated with M2 macrophage polarization and could potentially contribute to this phenotypic shift, a process that may play a critical role in the immunological mechanisms underlying tuberculosis pathogenesis.