Macrophage migration inhibitory factor of Thelazia callipaeda induces M2-like macrophage polarization through TLR4-mediated activation of the PI3K-Akt pathway
Macrophage migration inhibitory factor of Thelazia callipaeda induces M2-like macrophage polarization through TLR4-mediated activation of the PI3K-Akt pathway
复制标题
吸吮线虫巨噬细胞迁移抑制因子通过 TLR4 介导的 PI3K-Akt 通路激活诱导 M2 样巨噬细胞极化
DOI：
10.1096/fj.202100676r
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发表时间：
2021-09-01
期刊：
影响因子：
4.8
通讯作者：
Liu, Hui
中科院分区：
文献类型：
--
作者：
Cai, Juan;Huang, Lin;Liu, Hui
巨噬细胞移动抑制因子（MIF）是一种免疫调节细胞因子，在炎症和免疫应答中起重要作用，并且已被描述为在寄生虫的免疫逃避中具有潜在作用。摘要美足吸吮线虫是一种媒介传播的人畜共患眼虫，具有广泛的宿主范围，是引起眼部吸吮线虫病的病原。T.丽翅虫能够在有免疫能力的宿主中持续存在，这表明它已经进化出了对抗免疫防御的特定措施。迄今为止，T. Callipaeda与MIF有关，可能的相关信号通路和分子机制尚不清楚。在本研究中，我们研究了T。callipaeda MIF（T. cp-MIF）对巨噬细胞的作用。我们分析了候选T. cp-MIF具有理想的抗原性。形态学、流式细胞术和细胞因子分析显示T. cp-MIF诱导THP-1巨噬细胞从M1样表型动态极化为M2样表型。趋化实验显示T. cp-MIF对THP-1巨噬细胞的作用。Western blotting结果显示，与对照组相比，T. cp-MIF具有更高的TLR 4蛋白表达和磷脂酰肌醇3 '-激酶（PI 3 K）-Akt通路激活。总之，T. cp-MIF通过TLR 4介导的PI 3 K-Akt通路的激活诱导M2样巨噬细胞极化，这可能为将来研究其如何影响宿主免疫系统提供基础。
Macrophage migration inhibitory factor (MIF), an immunoregulatory cytokine plays an important role in inflammation and the immune response, and has been described as having a potential role in immune evasion by parasites. Thelazia callipaeda, a vector-borne zoonotic eye worm with a broad host range, has been documented as an agent of ocular infection of thelaziosis. The ability of T. callipaeda to persist in an immunologically competent host has led to the suggestion that it has evolved specific measures to counter immune defenses. To date, whether the immune evasion of T. callipaeda is related to MIF and the possible related signaling pathway and molecular mechanism have remained unclear. In the present study, we examined the effect of T. callipaeda MIF (T. cp-MIF) on macrophages. We analyzed the antigenic epitopes of the candidate T. cp-MIF and found that it exhibited an ideal antigenic index. Morphology, Flow cytometry, and cytokine analysis showed that T. cp-MIF induced the dynamic polarization of THP-1 macrophages from the M1-like phenotype to the M2-like phenotype. The chemotaxis assay revealed an inhibitory effect of T. cp-MIF on THP-1 macrophages. Western blotting suggested that, compared to the control, THP-1 macrophages exposed to T. cp-MIF had higher TLR4 protein expression and the phosphatidylinositol 3 '-kinase (PI3K) -Akt pathway activation. In conclusion, T. cp-MIF induces M2-like macrophage polarization through TLR4-mediated activation of the PI3K-Akt pathway, which might provide a basis for future research on how it affects the immune system of the host.