Related Experiment Video
Updated: Feb 26, 2026
Macrophage Differentiation and Polarization into an M2-Like Phenotype using a Human Monocyte-Like THP-1 Leukemia Cell Line
Published on: August 2, 2021
The Mincle ligand trehalose dibehenate differentially modulates M1-like and M2-like macrophage phenotype and function
Kristel Kodar1,2, Jacquie L Harper2, Melanie J McConnell3
1School of Chemical and Physical Sciences, Victoria University of Wellington, PO Box 600, Wellington, New Zealand.
Introduction:
Macrophages play a significant role in the progression of diseases, such as cancer, making them a target for immune-modulating agents. Trehalose dibehenate (TDB) is known to activate M1-like macrophages via Mincle, however, the effect of TDB on M2-like macrophages, which are found in the tumor microenvironment, has not been studied.
Methods:
qRT-PCR, flow cytometry, cytokine ELISA, and Western Blotting were used to study the effect of TDB on GM-CSF and M-CSF/IL-4 derived bone marrow macrophages (BMMs) from C57BL/6 and Mincle-/- mice.
Results:
TDB treatment up-regulated M1 markers over M2 markers by GM-CSF BMMs, whereas M-CSF/IL-4 BMMs down-regulated marker gene expression overall. TDB treatment resulted in Mincle-independent down-regulation of CD11b, CD115, and CD206 expression by GM-CSF macrophages and CD115 in M-CSF/IL-4 macrophages. GM-CSF BMMs produced of significant levels of proinflammatory cytokines (IL-1β, IL-6, TNF-α), which was Mincle-dependent and further enhanced by LPS priming. M-CSF BMMs produced little or no cytokines in response to TDB regardless of LPS priming. Western blot analysis confirmed that the absence of cytokine production was associated with a lack of activation of the Syk kinase pathway.
Conclusion:
This study illustrates that TDB has the potential to differentially regulate M1- and M2-like macrophages in the tumor environment.
