Upregulation of CREB1 by Mycobacterium Tuberculosis Transcriptionally Activates TREM2 to Promote Macrophage M2 Polarization.

Authors

Yufeng Zhu, Mingzhong Xu, Danxia Liu, Wei Ning, Miaomiao Wang, Feifan Huang, Zhen An, Jingsong Qiu, Xian Tang, Peipei Wang, Bin Tian, Lan Wen

Published in

Cell biochemistry and function. Volume 44. Issue 8. Pages e70284.

Abstract

Tuberculosis, caused by Mycobacterium tuberculosis (MTB), affects approximately 25% of people globally as latent infection (LTBI). Although macrophage CREB activation promotes MTB survival, the underlying mechanisms remain unclear. This study reveals, for the first time, how MTB modulates M2 macrophage polarization through the CREB1/TREM2 signaling pathway. Mononuclear macrophages were isolated from clinical sample. Flow cytometry was used to determine the M2 polarization ratio. The expression of TNF-α, IL-10, and IL-1β was determined by ELISA. The mRNA expression of iNOS, IL-1β, CD206, Arg-1, IL-10, CREB1, and TREM2 was assessed by qPCR. The protein expression of CREB1, CD206, Arg-1, IL-10, and TREM2 was evaluated by western blot. The colony-forming unit (CFU) assay was used to detect the survival of MTB. CHIP and Dual-luciferase reporter assays were used to confirm the binding of CREB1 and TREM2. Clinical sample analysis revealed that the expression levels of CREB1 and TREM2 in peripheral blood mononuclear macrophages (PBMCs) were significantly upregulated in tuberculosis patients. Following H37Rv infection, an increase in the M2 macrophage proportion was observed. Infection with MTB also elevated the protein level of IL-10, as well as CREB1 mRNA and protein expression. Transfecting sh-CREB1 into macrophages or adding CREB inhibitors 666-15 markedly reduced intracellular MTB CFU counts, implying a potential restrictive effect on viable MTB load within macrophages. Knockdown of TREM2 similarly decreased MTB CFU burden and restrained macrophage M2 polarization. Furthermore, transfecting sh-CREB1 into macrophages can suppress the proliferation of MTB within macrophages, and these effects could be further counteracted by the action of oe-TREM2. These results elucidated that MTB promoted M2 macrophage polarization through CREB1/TREM2.

PMID:
42605552
Bibliographic data and abstract were imported from PubMed on 17 Aug 2026.

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