Laboratory of Vaccine Materials and Laboratory of Gut Environmental Health, Microbial Research Center for Health and Medicine, National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), Ibaraki, Osaka, Japan.
Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka, Japan.
Front Immunol. 2023 Apr 21;14:1111729. doi: 10.3389/fimmu.2023.1111729. eCollection 2023.
Macrophages manifest as various subtypes that play diverse and important roles in immunosurveillance and the maintenance of immunological homeostasis in various tissues. Many studies divide macrophages into two broad groups: M1 macrophages induced by lipopolysaccharide (LPS), and M2 macrophages induced by interleukin 4 (IL-4). However, considering the complex and diverse microenvironment , the concept of M1 and M2 is not enough to explain diversity of macrophages. In this study, we analyzed the functions of macrophages induced by simultaneous stimulation with LPS and IL-4 (termed LPS/IL-4-induced macrophages). LPS/IL-4-induced macrophages were a homogeneous population showing a mixture of the characteristics of M1 and M2 macrophages. In LPS/IL-4-induced macrophages, expression of cell-surface M1 markers (I-A) was higher than in M1 macrophages, but lower expression of iNOS, and expression of M1-associated genes ( and ) were decreased in comparison to expression in M1 macrophages. Conversely, expression of the cell-surface M2 marker CD206 was lower on LPS/IL-4-induced macrophages than on M2 macrophages and expression of M2-associated genes (, , and ) varied, with being greater than, being lower than, and being comparable to that in M2 macrophages. Glycolysis-dependent phagocytic activity of LPS/IL-4-induced macrophages was strongly enhanced as was that of M1 macrophages; however, the energy metabolism of LPS/IL-4-induced macrophages, such as activation state of glycolytic and oxidative phosphorylation, was quite different from that of M1 or M2 macrophages. These results indicate that the macrophages induced by LPS and IL-4 had unique properties.
巨噬细胞表现为多种亚型，在各种组织的免疫监视和免疫稳态维持中发挥着多样化和重要的作用。许多研究将巨噬细胞分为两大类：由脂多糖 (LPS) 诱导的 M1 巨噬细胞和由白细胞介素 4 (IL-4) 诱导的 M2 巨噬细胞。然而，考虑到复杂多样的微环境，M1 和 M2 的概念不足以解释巨噬细胞的多样性。在本研究中，我们分析了同时受到 LPS 和 IL-4 刺激诱导的巨噬细胞（称为 LPS/IL-4 诱导的巨噬细胞）的功能。LPS/IL-4 诱导的巨噬细胞是一个同质群体，表现出 M1 和 M2 巨噬细胞特征的混合。在 LPS/IL-4 诱导的巨噬细胞中，细胞表面 M1 标志物 (I-A) 的表达高于 M1 巨噬细胞，但 iNOS 的表达较低，并且与 M1 巨噬细胞相比，M1 相关基因 (和) 的表达降低。相反，LPS/IL-4 诱导的巨噬细胞表面的 M2 标志物 CD206 的表达低于 M2 巨噬细胞，并且 M2 相关基因 (、和) 的表达存在差异，其中 大于、小于和等于 M2 巨噬细胞。LPS/IL-4 诱导的巨噬细胞的糖酵解依赖性吞噬活性与 M1 巨噬细胞一样强烈增强；然而，LPS/IL-4 诱导的巨噬细胞的能量代谢，如糖酵解和氧化磷酸化的激活状态，与 M1 或 M2 巨噬细胞有很大不同。这些结果表明，LPS 和 IL-4 诱导的巨噬细胞具有独特的特性。
