Polarization of mouse macrophages towards M1 and M2b types induced by outer membrane vesicles derived from <i>Proteus mirabilis</i>

WEI Junzhi; LIU Shijia; ZONG Yongtai; ZHANG Hong; TAN Yao

doi:10.15886/j.cnki.rdswxb.20240039

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Volume 15 Issue 4

Jul. 2024

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Article Navigation > Journal of Tropical Biology > 2024 > 15(4): 445-451

WEI Junzhi, LIU Shijia, ZONG Yongtai, ZHANG Hong, TAN Yao. Polarization of mouse macrophages towards M1 and M2b types induced by outer membrane vesicles derived from Proteus mirabilis[J]. Journal of Tropical Biology, 2024, 15(4): 445-451. doi: 10.15886/j.cnki.rdswxb.20240039

Citation:

WEI Junzhi, LIU Shijia, ZONG Yongtai, ZHANG Hong, TAN Yao. Polarization of mouse macrophages towards M1 and M2b types induced by outer membrane vesicles derived from Proteus mirabilis[J]. Journal of Tropical Biology, 2024, 15(4): 445-451. doi: 10.15886/j.cnki.rdswxb.20240039

Polarization of mouse macrophages towards M1 and M2b types induced by outer membrane vesicles derived from Proteus mirabilis

doi: 10.15886/j.cnki.rdswxb.20240039

1. School of Tropical Agriculture and Forestry, Hainan University, Haikou, 570228, China;
2. School of Animal Science and Technology, Anhui Agricultural University, Hefei, 230036, China

Received Date: 2024-03-12
Rev Recd Date: 2024-03-25
Publish Date: 2024-07-25

Abstract

To investigate whether bacterial outer membrane vesicles（OMVs） secreted by the conditionally pathogenic bacterium Proteus mirabilis have the function of inducing macrophage polarization to regulate the tumor microenvironment, the mouse macrophage RAW264.7 was stimulated with the OMVs to detect macrophage polarization-related phenotype. The OMVs were isolated, extracted and then characterized using transmission electron microscopy. The OMVs were traced with PKH67 fluorescent dye, and the uptake of OMVs by RAW264.7cells was observed by using fluorescence microscopy. The total NO content secreted by RAW264.7 cells and the expression of polarization-associated factors in RAW264.7 cells were detected by using total nitric oxide（NO）detection kit and real-time fluorescence quantitative PCR（RT-qPCR）, respectively. The results showed that OMVs could be taken up by RAW264.7 cells, induced an increase in NO secretion in these cells, and upregulated the expression of IL-10, IL-1β, TNF1-α, and IL-6, i. e., the occurrence of M1-type and M2b-type polarizations, which activated anti-tumor activity of macrophages. The above results suggest a potential role of OMVs secreted by P. mirabilis in the bacterium’s resistance to breast tumor growth and lung metastasis.
- Proteus mirabilis,
- Bacterial outer membrane vesicles,
- macrophages

References

[1]	STARNES C O. Coley’s toxins[J]. Nature, 1992, 360:23.
[2]	陈欧亮,张红,赵鑫铖,等.细菌外膜囊泡的抗肿瘤机制及其应用研究进展[J].动物医学进展, 2022, 43(9):85-89.
[3]	ZHANG H, DIAO H, JIA L, et al. Proteus mirabilis inhibits cancer growth and pulmonary metastasis in a mouse breast cancer model[J]. PLoS One, 2017, 12(12):e0188960.
[4]	ZHANG H, SANG S, XU H, et al. Lovastatin suppresses bacterial therapy-induced neutrophil recruitment to the tumor by promoting neutrophil apoptosis[J]. Journal of Functional Foods, 2021, 86:104693.
[5]	隋阳,赵治宇,吴长君.肿瘤相关巨噬细胞在三阴性乳腺癌中的研究进展[J].中国免疫学杂志, 2023, 39(2):444-448.
[6]	王玉玮,杨长青,魏子白,等.肿瘤相关巨噬细胞与胃癌的研究进展[J].临床医药实践, 2023, 32(2):121-124.
[7]	卢昕雅,孔令慧.肿瘤免疫微环境中的免疫细胞与肺癌关系的研究进展[J].癌症进展, 2023, 21(7):703-706.
[8]
[9]	叶润发,王淳,韩东河,等.小胶质细胞和巨噬细胞极化与多发性硬化症的研究进展[J].医学研究生学报,2021, 34(7):761-764.
[10]	王硕,彭欢,田锐.免疫调节在急性心肌梗死后炎症导致心肌重构的治疗进展[J].心肺血管病杂志, 2022,41(9):1018-1022.
[11]	罗维,景涛,戴剑松.代谢性疾病中巨噬细胞极化的机制及运动对其调控作用的研究进展[J].中国免疫学杂志, 2023, 39(2):421-426.
[12]	邢薿文,谢言,覃尧.脂多糖刺激的鸡巨噬细胞源外体对文昌鸡树突状细胞的活化作用[J].热带生物学报,2023, 14(4):433-440.
[13]	GUERRERO-MANDUJANO A, HERNÁNDEZ-CORTEZ C, IBARRA J A, et al. The outer membrane vesicles:secretion system type zero[J]. Traffic, 2017, 18(7):425-432.
[14]	SARTORIO M G, PARDUE E J, FELDMAN M F, et al.Bacterial outer membrane vesicles:from discovery to applications[J]. Annual Review of Microbiology, 2021,75:609-630.
[15]	姚崧源,孙述学.细菌外膜囊泡在疫苗领域的研究进展[J].微生物学免疫学进展, 2021, 49(1):78-82.
[16]	杨霞,宁宗.巨噬细胞极化调控信号通路及M1/M2失衡在肺部炎症性疾病中作用的研究进展[J].山东医药, 2023, 63(26):88-91.
[17]	CHEN Q, BAI H, WU W, et al. Bioengineering bacterial vesicle-coated polymeric nanomedicine for enhanced cancer immunotherapy and metastasis prevention[J].Nano Letters, 2020, 20(1):11-21.
[18]	LI M, ZHOU H, YANG C, et al. Bacterial outer membrane vesicles as a platform for biomedical applications:an update[J]. Journal of Controlled Release:Official Journal of the Controlled Release Society, 2020, 323:253-268.
[19]	ANDERSON C F, MOSSER D M. A novel phenotype for an activated macrophage:the type 2 activated macrophage[J].Journal of Leukocyte Biology, 2002, 72(1):101-106.
[20]	WANG L X, ZHANG S X, WU H J, et al. M2b macrophage polarization and its roles in diseases[J]. Journal of Leukocyte Biology, 2019, 106(2):345-358.
[21]	ZHANG Q, SIOUD M. Tumor-associated macrophage subsets:shaping polarization and targeting[J]. International Journal of Molecular Sciences, 2023, 24(8):7493.
[22]	ITO I, ASAI A, SUZUKI S, et al. M2b macrophage polarization accompanied with reduction of long noncoding RNA GAS5[J]. Biochemical and Biophysical Research Communications, 2017, 493(1):170-175.
[23]	ASAI A, TSUCHIMOTO Y, OHAMA H, et al. Host antitumor resistance improved by the macrophage polarization in a chimera model of patients with HCC[J]. Oncoimmunology, 2017, 6(4):e1299301.
[24]	丁祝进,崔虎军,谷昭天,等.鱼类巨噬细胞标记物的研究进展[J].水产科学, 2023, 42(3):517-526.
[25]	BOSCO M C. Macrophage polarization:reaching across the aisle?[J]. The Journal of Allergy and Clinical Immunology, 2019, 143(4):1348-1350.
[26]	CHENG K, ZHAO R, LI Y, et al. Bioengineered bacteriaderived outer membrane vesicles as a versatile antigen display platform for tumor vaccination via Plug-andDisplay technology[J]. Nature Communications, 2021,12(1):2041.
[27]	SCHETTERS S T T, JONG W S P, HORREVORTS S K,et al. Outer membrane vesicles engineered to express membrane-bound antigen program dendritic cells for cross-presentation to CD8+T cells[J]. Acta Biomaterialia,2019, 91:248-257.

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通讯作者: 陈斌, bchen63@163.com

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沈阳化工大学材料科学与工程学院沈阳 110142

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Polarization of mouse macrophages towards M1 and M2b types induced by outer membrane vesicles derived from Proteus mirabilis

1. School of Tropical Agriculture and Forestry, Hainan University, Haikou, 570228, China;

2. School of Animal Science and Technology, Anhui Agricultural University, Hefei, 230036, China

Received Date: 2024-03-12

Rev Recd Date: 2024-03-25

Publish Date: 2024-07-25

Key words:

Abstract: To investigate whether bacterial outer membrane vesicles（OMVs） secreted by the conditionally pathogenic bacterium Proteus mirabilis have the function of inducing macrophage polarization to regulate the tumor microenvironment, the mouse macrophage RAW264.7 was stimulated with the OMVs to detect macrophage polarization-related phenotype. The OMVs were isolated, extracted and then characterized using transmission electron microscopy. The OMVs were traced with PKH67 fluorescent dye, and the uptake of OMVs by RAW264.7cells was observed by using fluorescence microscopy. The total NO content secreted by RAW264.7 cells and the expression of polarization-associated factors in RAW264.7 cells were detected by using total nitric oxide（NO）detection kit and real-time fluorescence quantitative PCR（RT-qPCR）, respectively. The results showed that OMVs could be taken up by RAW264.7 cells, induced an increase in NO secretion in these cells, and upregulated the expression of IL-10, IL-1β, TNF1-α, and IL-6, i. e., the occurrence of M1-type and M2b-type polarizations, which activated anti-tumor activity of macrophages. The above results suggest a potential role of OMVs secreted by P. mirabilis in the bacterium’s resistance to breast tumor growth and lung metastasis.

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Reference (27)

[1]	STARNES C O. Coley’s toxins[J]. Nature, 1992, 360:23.
[2]	陈欧亮,张红,赵鑫铖,等.细菌外膜囊泡的抗肿瘤机制及其应用研究进展[J].动物医学进展, 2022, 43(9):85-89.
[3]	ZHANG H, DIAO H, JIA L, et al. Proteus mirabilis inhibits cancer growth and pulmonary metastasis in a mouse breast cancer model[J]. PLoS One, 2017, 12(12):e0188960.
[4]	ZHANG H, SANG S, XU H, et al. Lovastatin suppresses bacterial therapy-induced neutrophil recruitment to the tumor by promoting neutrophil apoptosis[J]. Journal of Functional Foods, 2021, 86:104693.
[5]	隋阳,赵治宇,吴长君.肿瘤相关巨噬细胞在三阴性乳腺癌中的研究进展[J].中国免疫学杂志, 2023, 39(2):444-448.
[6]	王玉玮,杨长青,魏子白,等.肿瘤相关巨噬细胞与胃癌的研究进展[J].临床医药实践, 2023, 32(2):121-124.
[7]	卢昕雅,孔令慧.肿瘤免疫微环境中的免疫细胞与肺癌关系的研究进展[J].癌症进展, 2023, 21(7):703-706.
[8]
[9]	叶润发,王淳,韩东河,等.小胶质细胞和巨噬细胞极化与多发性硬化症的研究进展[J].医学研究生学报,2021, 34(7):761-764.
[10]	王硕,彭欢,田锐.免疫调节在急性心肌梗死后炎症导致心肌重构的治疗进展[J].心肺血管病杂志, 2022,41(9):1018-1022.
[11]	罗维,景涛,戴剑松.代谢性疾病中巨噬细胞极化的机制及运动对其调控作用的研究进展[J].中国免疫学杂志, 2023, 39(2):421-426.
[12]	邢薿文,谢言,覃尧.脂多糖刺激的鸡巨噬细胞源外体对文昌鸡树突状细胞的活化作用[J].热带生物学报,2023, 14(4):433-440.
[13]	GUERRERO-MANDUJANO A, HERNÁNDEZ-CORTEZ C, IBARRA J A, et al. The outer membrane vesicles:secretion system type zero[J]. Traffic, 2017, 18(7):425-432.
[14]	SARTORIO M G, PARDUE E J, FELDMAN M F, et al.Bacterial outer membrane vesicles:from discovery to applications[J]. Annual Review of Microbiology, 2021,75:609-630.
[15]	姚崧源,孙述学.细菌外膜囊泡在疫苗领域的研究进展[J].微生物学免疫学进展, 2021, 49(1):78-82.
[16]	杨霞,宁宗.巨噬细胞极化调控信号通路及M1/M2失衡在肺部炎症性疾病中作用的研究进展[J].山东医药, 2023, 63(26):88-91.
[17]	CHEN Q, BAI H, WU W, et al. Bioengineering bacterial vesicle-coated polymeric nanomedicine for enhanced cancer immunotherapy and metastasis prevention[J].Nano Letters, 2020, 20(1):11-21.
[18]	LI M, ZHOU H, YANG C, et al. Bacterial outer membrane vesicles as a platform for biomedical applications:an update[J]. Journal of Controlled Release:Official Journal of the Controlled Release Society, 2020, 323:253-268.
[19]	ANDERSON C F, MOSSER D M. A novel phenotype for an activated macrophage:the type 2 activated macrophage[J].Journal of Leukocyte Biology, 2002, 72(1):101-106.
[20]	WANG L X, ZHANG S X, WU H J, et al. M2b macrophage polarization and its roles in diseases[J]. Journal of Leukocyte Biology, 2019, 106(2):345-358.
[21]	ZHANG Q, SIOUD M. Tumor-associated macrophage subsets:shaping polarization and targeting[J]. International Journal of Molecular Sciences, 2023, 24(8):7493.
[22]	ITO I, ASAI A, SUZUKI S, et al. M2b macrophage polarization accompanied with reduction of long noncoding RNA GAS5[J]. Biochemical and Biophysical Research Communications, 2017, 493(1):170-175.
[23]	ASAI A, TSUCHIMOTO Y, OHAMA H, et al. Host antitumor resistance improved by the macrophage polarization in a chimera model of patients with HCC[J]. Oncoimmunology, 2017, 6(4):e1299301.
[24]	丁祝进,崔虎军,谷昭天,等.鱼类巨噬细胞标记物的研究进展[J].水产科学, 2023, 42(3):517-526.
[25]	BOSCO M C. Macrophage polarization:reaching across the aisle?[J]. The Journal of Allergy and Clinical Immunology, 2019, 143(4):1348-1350.
[26]	CHENG K, ZHAO R, LI Y, et al. Bioengineered bacteriaderived outer membrane vesicles as a versatile antigen display platform for tumor vaccination via Plug-andDisplay technology[J]. Nature Communications, 2021,12(1):2041.
[27]	SCHETTERS S T T, JONG W S P, HORREVORTS S K,et al. Outer membrane vesicles engineered to express membrane-bound antigen program dendritic cells for cross-presentation to CD8+T cells[J]. Acta Biomaterialia,2019, 91:248-257.

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Polarization of mouse macrophages towards M1 and M2b types induced by outer membrane vesicles derived from Proteus mirabilis

doi: 10.15886/j.cnki.rdswxb.20240039

Abstract

References

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通讯作者: 陈斌, bchen63@163.com

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Polarization of mouse macrophages towards M1 and M2b types induced by outer membrane vesicles derived from Proteus mirabilis

doi: 10.15886/j.cnki.rdswxb.20240039

1. School of Tropical Agriculture and Forestry, Hainan University, Haikou, 570228, China;

2. School of Animal Science and Technology, Anhui Agricultural University, Hefei, 230036, China

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Polarization of mouse macrophages towards M1 and M2b types induced by outer membrane vesicles derived from Proteus mirabilis

doi: 10.15886/j.cnki.rdswxb.20240039

Abstract

References

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通讯作者: 陈斌, bchen63@163.com

Proportional views

Related

Polarization of mouse macrophages towards M1 and M2b types induced by outer membrane vesicles derived from Proteus mirabilis

doi: 10.15886/j.cnki.rdswxb.20240039

1. School of Tropical Agriculture and Forestry, Hainan University, Haikou, 570228, China; 2. School of Animal Science and Technology, Anhui Agricultural University, Hefei, 230036, China

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1. School of Tropical Agriculture and Forestry, Hainan University, Haikou, 570228, China;

2. School of Animal Science and Technology, Anhui Agricultural University, Hefei, 230036, China