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Yeast (Saccharomyces cerevisiae) Polarizes Both M-CSF- and GM-CSF-Differentiated Macrophages Toward an M1-Like Phenotype

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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.

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Acknowledgments

We would like to thank Prof. Dr. Leon Abelmann (KIST Europe) and Prof. Dr. Andreas Manz (KIST Europe) for their continuous support. This work was funded by the KIST-Europe basic research program (11402) and the DFG (KI702).

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Authors and Affiliations

  1. Korea Institute of Science and Technology Europe, Saarbruecken, Germany

    Michelle Seif & Anja Philippi

  2. Molecular and Cell Biology, Saarland University, Saarbruecken, Germany

    Frank Breinig

  3. Department of Pharmacy, Pharmaceutical Biology, Saarland University, Campus C2 3, 66123, Saarbruecken, Germany

    Alexandra K. Kiemer & Jessica Hoppstädter

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  1. Michelle Seif
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Correspondence to Jessica Hoppstädter.

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Seif, M., Philippi, A., Breinig, F. et al. Yeast (Saccharomyces cerevisiae) Polarizes Both M-CSF- and GM-CSF-Differentiated Macrophages Toward an M1-Like Phenotype. Inflammation 39, 1690–1703 (2016). https://doi.org/10.1007/s10753-016-0404-5

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