Department of Parasitology, Zunyi Medical University, Zunyi, China.
Front Immunol. 2023 Jan 11;13:1078880. doi: 10.3389/fimmu.2022.1078880. eCollection 2022.
Macrophages are innate immune cells with essential roles in the immune response during helminth infection. Particularly, the direction of macrophage polarization could contribute to pathogen trapping and killing as well as tissue repair and the resolution of type 2 inflammation. This study establishes that the recombinant protein of macrophage migration inhibitory factor (-MIF) induces THP-1-derived macrophages to undergo M1 to M2 type dynamic polarization, using the methods of flow cytometry, real-time quantitative PCR, differential transcriptomic analysis and western blot. Interestingly, there was an increase in protein and mRNA expression of M1-type proteins and cytokines after the use of PI3K inhibitors, suggesting that the polarization state tends to favor the M1 type after M2 type inhibition. In conclusion, the dynamic polarization mechanism of -MIF-induced human THP-1-derived macrophages from M1 to M2 type is related to the binding of TLR4. It can first affect the M1 type polarization of macrophages by activating its downstream NF-κB pathway. Activation of the PI3K/Akt pathway and inhibition of NF-κB phosphorylation affects the M2 type polarization of macrophages.
巨噬细胞是先天免疫细胞,在寄生虫感染期间的免疫反应中具有重要作用。特别是,巨噬细胞极化的方向有助于病原体的捕获和杀伤,以及组织修复和 2 型炎症的消退。本研究通过流式细胞术、实时定量 PCR、差异转录组分析和 Western blot 等方法,证实了巨噬细胞移动抑制因子(-MIF)的重组蛋白可诱导 THP-1 衍生的巨噬细胞发生 M1 到 M2 型的动态极化。有趣的是,使用 PI3K 抑制剂后,M1 型蛋白和细胞因子的蛋白和 mRNA 表达增加,表明在抑制 M2 型后,极化状态倾向于有利于 M1 型。总之,-MIF 诱导人 THP-1 衍生巨噬细胞从 M1 到 M2 型的动态极化机制与 TLR4 的结合有关。它可以通过激活其下游 NF-κB 通路,首先影响巨噬细胞的 M1 型极化。激活 PI3K/Akt 通路和抑制 NF-κB 磷酸化会影响巨噬细胞的 M2 型极化。