Anti-Tumoral Effect and Action Mechanism of Exosomes Derived From Toxoplasma gondii-Infected Dendritic Cells in Mice Colorectal Cancer

文献类型： 外文期刊

第一作者： Zhu, Shilan

作者： Zhu, Shilan;Lu, Jinmiao;Abuzeid, Asmaa M. I.;Chen, Xiaoyu;Zhuang, Tingting;Li, Guoqing;Zhu, Shilan;Lu, Jinmiao;Chen, Xiaoyu;Gong, Haiyan;Mi, Rongsheng;Huang, Yan;Chen, Zhaoguo;Lin, Zhibing;Abuzeid, Asmaa M. I.

作者机构：

关键词： Toxoplasma gondii; dendritic cells; exosome; miRNA; macrophage; miR-155-5p

期刊名称：FRONTIERS IN ONCOLOGY （ 影响因子：5.738； 五年影响因子：6.122 ）

ISSN： 2234-943X

年卷期： 2022 年 12 卷

页码：

收录情况： SCI

摘要： Toxoplasma gondii is an obligate intracellular protozoan with anti-tumor activity against a variety of cancers. However, the therapeutic effect of T. gondii on colorectal cancer is unclear, and using direct Toxoplasma infection in immunotherapy involves safety concerns. This study investigated the anti-tumoral effect and mechanism of exosomes derived from dendritic cells (DCs) infected with T. gondii (Me49-DC-Exo). We used differential ultracentrifugation to isolate exosomes from uninfected DCs (DC-Exo) and T. gondii Me49-infected DCs (Me49-DC-Exo). The isolated exosomes were identified by transmission electron microscopy, nanoparticle tracking analysis, and western blotting. Me49-DC-Exo significantly inhibited the tumor growth and reduced the proportion of M2 macrophages in the blood of tumor-bearing mice. In vitro, Me49-DC-Exo suppressed macrophage (RAW264.7) polarization to M2 phenotype. miRNA sequencing revealed that multiple miRNAs in Me49-DC-Exo were differentially expressed compared with DC-Exo, among which miR-182-5p, miR-155-5p, miR-125b-2-3p, and miR-155-3p were up-regulated, while miR-9-5p was significantly down-regulated. Transfecting mimics or inhibitors of these differential miRNAs into RAW264.7 cells showed that miR-155-5p promoted M1 macrophage polarization while inhibiting M2 macrophage polarization. Bioinformatics prediction and dual-luciferase reporter assay confirmed the suppressor of cytokine signaling 1 (SOCS1) as a direct target of miR-155-5p. Silencing SOCS1 gene expression in RAW264.7 cells increased CD86 (+) CD206 (-) M1 macrophage proportion, and inducible nitric oxide synthase and tumor necrosis factor-alpha mRNA levels. However, arginase-1 and transglutaminase 2 expression levels decreased. These results suggest that the exosomes inhibit macrophage polarization to M2 phenotype and regulate SOCS1 expression by delivering functional miR-155-5p. These findings provide new ideas for colorectal cancer immunotherapy.

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