Medicinal plant-derived mtDNA via nanovesicles induces the cGAS-STING pathway to remold tumor-associated macrophages for tumor regression
Abstract Plant-derived nanovesicles (PDNVs) have been proposed as a major mechanism for the inter-kingdom interaction and communication, but the effector components enclosed in the vesicles and the mechanisms involved are largely unknown. The plant Artemisia annua is known as an anti-malaria agent t...
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| Format: | Article |
| Language: | English |
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BMC
2023-03-01
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| Series: | Journal of Nanobiotechnology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12951-023-01835-0 |
| _version_ | 1797863667389169664 |
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| author | Jinfeng Liu Jiaxin Xiang Cuiyuan Jin Lusha Ye Lei Wang Yanan Gao Nianyin Lv Junfeng Zhang Fuping You Hongzhi Qiao Liyun Shi |
| author_facet | Jinfeng Liu Jiaxin Xiang Cuiyuan Jin Lusha Ye Lei Wang Yanan Gao Nianyin Lv Junfeng Zhang Fuping You Hongzhi Qiao Liyun Shi |
| author_sort | Jinfeng Liu |
| collection | DOAJ |
| description | Abstract Plant-derived nanovesicles (PDNVs) have been proposed as a major mechanism for the inter-kingdom interaction and communication, but the effector components enclosed in the vesicles and the mechanisms involved are largely unknown. The plant Artemisia annua is known as an anti-malaria agent that also exhibits a wide range of biological activities including the immunoregulatory and anti-tumor properties with the mechanisms to be further addressed. Here, we isolated and purified the exosome-like particles from A. annua, which were characterized by nano-scaled and membrane-bound shape and hence termed artemisia-derived nanovesicles (ADNVs). Remarkably, the vesicles demonstrated to inhibit tumor growth and boost anti-tumor immunity in a mouse model of lung cancer, primarily through remolding the tumor microenvironment and reprogramming tumor-associated macrophages (TAMs). We identified plant-derived mitochondrial DNA (mtDNA), upon internalized into TAMs via the vesicles, as a major effector molecule to induce the cGAS-STING pathway driving the shift of pro-tumor macrophages to anti-tumor phenotype. Furthermore, our data showed that administration of ADNVs greatly improved the efficacy of PD-L1 inhibitor, a prototypic immune checkpoint inhibitor, in tumor-bearing mice. Together, the present study, for the first time, to our knowledge, unravels an inter-kingdom interaction wherein the medical plant-derived mtDNA, via the nanovesicles, induces the immunostimulatory signaling in mammalian immune cells for resetting anti-tumor immunity and promoting tumor eradication. Graphical Abstract |
| first_indexed | 2024-04-09T22:39:11Z |
| format | Article |
| id | doaj.art-4340a5697590498e864c6ff5a1fb562e |
| institution | Directory Open Access Journal |
| issn | 1477-3155 |
| language | English |
| last_indexed | 2024-04-09T22:39:11Z |
| publishDate | 2023-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj.art-4340a5697590498e864c6ff5a1fb562e2023-03-22T12:16:33ZengBMCJournal of Nanobiotechnology1477-31552023-03-0121111910.1186/s12951-023-01835-0Medicinal plant-derived mtDNA via nanovesicles induces the cGAS-STING pathway to remold tumor-associated macrophages for tumor regressionJinfeng Liu0Jiaxin Xiang1Cuiyuan Jin2Lusha Ye3Lei Wang4Yanan Gao5Nianyin Lv6Junfeng Zhang7Fuping You8Hongzhi Qiao9Liyun Shi10Department of Immunology, School of Medicine and Holistic Integrative Medicine, Nanjing University of Chinese MedicineDepartment of Immunology, School of Medicine and Holistic Integrative Medicine, Nanjing University of Chinese MedicineInstitute of Translational Medicine, Zhejiang Shuren UniversityDepartment of Immunology, School of Medicine and Holistic Integrative Medicine, Nanjing University of Chinese MedicineDepartment of Immunology, School of Medicine and Holistic Integrative Medicine, Nanjing University of Chinese MedicineDepartment of Immunology, School of Medicine and Holistic Integrative Medicine, Nanjing University of Chinese MedicineDepartment of Immunology, School of Medicine and Holistic Integrative Medicine, Nanjing University of Chinese MedicineDepartment of Immunology, School of Medicine and Holistic Integrative Medicine, Nanjing University of Chinese MedicineInstitute of Systems Biomedicine, Department of Immunology, School of Basic Medical Sciences, Beijing Key Laboratory of Tumor Systems Biology, NHC Key Laboratory of Medical Immunology, Peking University Health Science CenterJiangsu Key Laboratory for Functional Substance of Chinese Medicine, Jiangsu Engineering Research Center for Efficient Delivery System of TCM, School of Pharmacy, Nanjing University of Chinese MedicineDepartment of Immunology, School of Medicine and Holistic Integrative Medicine, Nanjing University of Chinese MedicineAbstract Plant-derived nanovesicles (PDNVs) have been proposed as a major mechanism for the inter-kingdom interaction and communication, but the effector components enclosed in the vesicles and the mechanisms involved are largely unknown. The plant Artemisia annua is known as an anti-malaria agent that also exhibits a wide range of biological activities including the immunoregulatory and anti-tumor properties with the mechanisms to be further addressed. Here, we isolated and purified the exosome-like particles from A. annua, which were characterized by nano-scaled and membrane-bound shape and hence termed artemisia-derived nanovesicles (ADNVs). Remarkably, the vesicles demonstrated to inhibit tumor growth and boost anti-tumor immunity in a mouse model of lung cancer, primarily through remolding the tumor microenvironment and reprogramming tumor-associated macrophages (TAMs). We identified plant-derived mitochondrial DNA (mtDNA), upon internalized into TAMs via the vesicles, as a major effector molecule to induce the cGAS-STING pathway driving the shift of pro-tumor macrophages to anti-tumor phenotype. Furthermore, our data showed that administration of ADNVs greatly improved the efficacy of PD-L1 inhibitor, a prototypic immune checkpoint inhibitor, in tumor-bearing mice. Together, the present study, for the first time, to our knowledge, unravels an inter-kingdom interaction wherein the medical plant-derived mtDNA, via the nanovesicles, induces the immunostimulatory signaling in mammalian immune cells for resetting anti-tumor immunity and promoting tumor eradication. Graphical Abstracthttps://doi.org/10.1186/s12951-023-01835-0Artemisia-derived nanovesiclesTumor-associated macrophagesmtDNAcGAS-STING |
| spellingShingle | Jinfeng Liu Jiaxin Xiang Cuiyuan Jin Lusha Ye Lei Wang Yanan Gao Nianyin Lv Junfeng Zhang Fuping You Hongzhi Qiao Liyun Shi Medicinal plant-derived mtDNA via nanovesicles induces the cGAS-STING pathway to remold tumor-associated macrophages for tumor regression Journal of Nanobiotechnology Artemisia-derived nanovesicles Tumor-associated macrophages mtDNA cGAS-STING |
| title | Medicinal plant-derived mtDNA via nanovesicles induces the cGAS-STING pathway to remold tumor-associated macrophages for tumor regression |
| title_full | Medicinal plant-derived mtDNA via nanovesicles induces the cGAS-STING pathway to remold tumor-associated macrophages for tumor regression |
| title_fullStr | Medicinal plant-derived mtDNA via nanovesicles induces the cGAS-STING pathway to remold tumor-associated macrophages for tumor regression |
| title_full_unstemmed | Medicinal plant-derived mtDNA via nanovesicles induces the cGAS-STING pathway to remold tumor-associated macrophages for tumor regression |
| title_short | Medicinal plant-derived mtDNA via nanovesicles induces the cGAS-STING pathway to remold tumor-associated macrophages for tumor regression |
| title_sort | medicinal plant derived mtdna via nanovesicles induces the cgas sting pathway to remold tumor associated macrophages for tumor regression |
| topic | Artemisia-derived nanovesicles Tumor-associated macrophages mtDNA cGAS-STING |
| url | https://doi.org/10.1186/s12951-023-01835-0 |
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