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Macrophage Differentiation and Polarization into an M2-Like Phenotype using a Human Monocyte-Like THP-1 Leukemia Cell Line
Published on: August 2, 2021
Yeast (Saccharomyces cerevisiae) Polarizes Both M-CSF- and GM-CSF-Differentiated Macrophages Toward an M1-Like
Michelle Seif1, Anja Philippi1, Frank Breinig2
1Korea Institute of Science and Technology Europe, Saarbruecken, Germany.
Abstract:
Macrophages are a heterogeneous and plastic cell population with two main phenotypes: pro-inflammatory classically activated macrophages (M1) and anti-inflammatory alternatively activated macrophages (M2). Saccharomyces cerevisiae is a promising vehicle for the delivery of vaccines. It is well established that S. cerevisiae is taken up by professional phagocytic cells. However, the response of human macrophages to S. cerevisiae is ill-defined. In this study, we characterized the interaction between S. cerevisiae and M1- or M2-like macrophages. M1-like macrophages had a higher yeast uptake capacity than M2-like macrophages, but both cell types internalized opsonized yeast to the same extent. The M1 surface markers HLAII and CD86 were upregulated after yeast uptake in M1- and M2-like macrophages. Moreover, mRNA expression levels of pro-inflammatory cytokines, such as TNF-α, IL-12, and IL-6, increased, whereas the expression of anti-inflammatory mediators did not change. These results demonstrate that S. cerevisiae can target both M1 and M2 macrophages, paralleled by skewing toward an M1 phenotype. Thus, the use of yeast-based delivery systems might be a promising approach for the treatment of pathologic conditions that would benefit from the presence of M1-polarized macrophages, such as cancer.
Insights
Saccharomyces cerevisiae yeast targets both pro-inflammatory (M1) and anti-inflammatory (M2) macrophages. Yeast uptake promotes an M1-like phenotype, suggesting potential for M1-polarized macrophage therapies.
Area of Science:
- Immunology
- Cell Biology
- Microbiology
Background:
- Macrophages exist as M1 (pro-inflammatory) and M2 (anti-inflammatory) phenotypes.
- Saccharomyces cerevisiae is a potential vaccine delivery vehicle.
- Human macrophage response to S. cerevisiae is not well understood.
Purpose of the Study:
- To investigate the interaction between S. cerevisiae and M1/M2 macrophages.
- To determine how S. cerevisiae affects macrophage polarization.
Main Methods:
- Cultured M1-like and M2-like human macrophages.
- Assessed yeast uptake and surface marker expression (HLAII, CD86).
- Measured mRNA levels of pro-inflammatory and anti-inflammatory cytokines.
Main Results:
- M1 macrophages showed higher yeast uptake than M2 macrophages.
- Both M1 and M2 macrophages upregulated M1 surface markers (HLAII, CD86) after yeast uptake.
- Pro-inflammatory cytokine mRNA (TNF-α, IL-12, IL-6) increased, while anti-inflammatory mediators remained unchanged.
Conclusions:
- S. cerevisiae interacts with and polarizes both M1 and M2 macrophages towards an M1 phenotype.
- Yeast-based delivery systems show promise for conditions requiring M1-polarized macrophages, such as cancer.
