Korea Institute of Science and Technology Europe, Saarbruecken, Germany.
Molecular and Cell Biology, Saarland University, Saarbruecken, Germany.
Inflammation. 2016 Oct;39(5):1690-703. doi: 10.1007/s10753-016-0404-5.
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.
巨噬细胞是一种具有异质性和可塑性的细胞群体，有两种主要表型：促炎的经典激活型巨噬细胞（M1）和抗炎的替代激活型巨噬细胞（M2）。酿酒酵母是疫苗传递的有前途的载体。已经证实，酿酒酵母被专业吞噬细胞摄取。然而，人类巨噬细胞对酿酒酵母的反应尚不清楚。在这项研究中，我们描述了酿酒酵母与 M1 样或 M2 样巨噬细胞之间的相互作用。M1 样巨噬细胞的酵母摄取能力高于 M2 样巨噬细胞，但这两种细胞类型内化调理酵母的程度相同。在 M1 和 M2 样巨噬细胞中摄取酵母后，M1 表面标志物 HLAII 和 CD86 的表达上调。此外，促炎细胞因子（如 TNF-α、IL-12 和 IL-6）的 mRNA 表达水平增加，而抗炎介质的表达没有变化。这些结果表明，酿酒酵母可以靶向 M1 和 M2 巨噬细胞，并向 M1 表型倾斜。因此，使用基于酵母的传递系统可能是治疗受益于 M1 极化巨噬细胞存在的病理状况的一种有前途的方法，例如癌症。
