Study on the dynamic change of myeloid-derived suppressor cells proportion and cytokine expression in peripheral blood of mice infected with Echinococcus multilocularis

doi:10.12140/j.issn.1000-7423.2024.02.012

Abstract

Abstract:

Objective To analyze the dynamic changes in the proportion of myeloid-derived suppressor cells (MDSCs) and their subtypes in peripheral blood leukocytes of mice infected with Echinococcus multilocularis protoscoleces and detect the expression of cytokines related to MDSCs proliferation in the late-infected mice serum. Methods Twenty-four BALB/c mice were randomly divided into the infected group and the control group, with 12 mice in each group. Mice in the infected group were intraperitoneally injected with 1 200 E. multilocularis protoscoleces, while mice in the control group injected with the same volume of normal saline. Three mice from each group were randomly selected at 30, 90 and 180 days after infection to observe histomorphological changes in liver and spleen. Peripheral blood was collected from orbital venous plexus to prepare peripheral blood leukocytes. After incubation with externally labeled antibodies to CD11b, Gr-1, Ly6G and Ly6C, flow cytometry was used to detect the proportions of MDSCs, polymorphonuclear MDSCs (PMN-MDSCs) and monocytic MDSCs (M-MDSCs). Serum samples from both groups were collected 180 days after infection for determine the concentrations of interleukin-6 (IL-6), IL-13, tumor necrosis factor α (TNF-α) and granulocyte-macrophage colony-stimulating factor (GM-CSF) by ELISA assay. GraphPad Prism 9.0 software was utilized for graphical and statistical analysis; independent sample t-test was used for inter-group comparison. Results After E. multilocularis protoscoleces infection, cysts appeared in the liver of infected group mice 30 days after infection, and volume of cysts was increased over time. Spleen of infected group mice were enlaged over time 30, 90, and 180 days after infection. The results of flow cytometry showed that 30, 90 and 180 days after infection, the proportion of MDSCs in peripheral blood leukocytes of infected group were (13.2 ± 2.4)%, (15.7 ± 2.3)% and (41.3 ± 4.0)%, respectively. And the proportion of MDSCs in the control group were (12.4 ± 3.2)%, (6.0 ± 0.9)% and (22.3 ± 1.1)%, respectively. The infected group was significantly higher than the control group 90 and 180 days after infection (t = 3.949, 4.682; P < 0.05, 0.01). 30, 90 and 180 days after infection, the proportion of PMN-MDSCs in peripheral blood leukocytes of infected mice were (10.9 ± 2.1)%, (12.5 ± 2.4)% and (35.8 ± 3.6)%, respectively. And the proportion of PMN-MDSCs in the control group were (9.6 ± 3.1)%, (4.5 ± 0.6)% and (18.5 ± 0.6)%, respectively. The infected group was significantly higher than the control group 90 and 180 days after infection (t = 3.237, 4.788, P < 0.05, 0.01). 30, 90 and 180 days after infection, the proportion of M-MDSCs in peripheral blood leukocytes of infected mice were (1.8 ± 0.3)%, (1.1 ± 0.1)% and (4.6 ± 1.1)%, respectively. And the proportion of M-MDSCs in the control group were (2.3 ± 0.2)%, (0.5 ± 0.1)% and (3.4 ± 0.9)%, respectively. The infected group was significantly higher than the control group 90 days after infection (t = 3.246, P < 0.05). 180 days after infection, the concentrations of IL-6, IL-13, TNF-α and GM-CSF in the infected mice serum were (315.39 ± 13.58), (339.41 ± 13.35), (223.53 ± 27.49) and (262.31 ± 2.36) pg/ml, respectively, which were significantly higher than that of control group [(14.93 ± 0.55), (50.74 ± 0.88), (50.64 ± 1.64) and (115.28 ± 0.58) pg/ml] (t = 22.100, 21.580, 6.277, 60.460; P < 0.01, 0.01, 0.05, 0.01). Conclusion The proportion of MDSCs in peripheral blood leukocytes increased with time after E. multilocularis protoscoleces infection, mainly of PMN-MDSCs. The concentrations of serum IL-6, IL-13, TNF-α and GM-CSF increased of mice in the late stage of E. multilocularis protoscoleces infection, which may promote the proliferation and activation of MDSCs.

Key words: Echinococcus multilocularis, Protoscoleces, Myeloid-derived suppressor cell, Cytokine

CLC Number:

R532.32

SU Yaxin, JIANG Nan, ZHANG Xiaocheng, WANG Ying, JIANG Xiaofeng, HUO Lele, WANG Yaxue, CAO Jianping, SHEN Yujuan. Study on the dynamic change of myeloid-derived suppressor cells proportion and cytokine expression in peripheral blood of mice infected with Echinococcus multilocularis[J]. CHINESE JOURNAL OF PARASITOLOGY AND PARASITIC DISEASES, 2024, 42(2): 211-216.

Figures/Tables 2

References 23

[1]	Wen H, Vuitton L, Tuxun T, et al. Echinococcosis: advances in the 21st century[J]. Clin Microbiol Rev, 2019, 32(2): e00075.
[2]	World Health Organization. World health statistics 2018: monitoring health for the SDGs, sustainable development goals[M]. Geneva: WHO, 2018: 6-8.
[3]	Jenkins EJ, Schurer JM, Gesy KM. Old problems on a new playing field: helminth zoonoses transmitted among dogs, wildlife, and people in a changing northern climate[J]. Vet Parasitol, 2011, 182(1): 54-69. doi: 10.1016/j.vetpar.2011.07.015 pmid: 21802208
[4]	Wang JH, Müller S, Lin RY, et al. Depletion of FoxP3⁺ Tregs improves control of larval Echinococcus multilocularis infection by promoting co-stimulation and Th1/17 immunity[J]. Immun Inflamm Dis, 2017, 5(4): 435-447.
[5]	Marvel D, Gabrilovich DI. Myeloid-derived suppressor cells in the tumor microenvironment: expect the unexpected[J]. J Clin Invest, 2015, 125(9): 3356-3364. doi: 10.1172/JCI80005 pmid: 26168215
[6]	Condamine T, Mastio J, Gabrilovich DI. Transcriptional regulation of myeloid-derived suppressor cells[J]. J Leukoc Biol, 2015, 98(6): 913-922.
[7]	Gabrilovich DI. Myeloid-derived suppressor cells[J]. Cancer Immunol Res, 2017, 5(1): 3-8. doi: 10.1158/2326-6066.CIR-16-0297 pmid: 28052991
[8]	Pan W, Zhou HJ, Shen YJ, et al. Surveillance on the status of immune cells after Echinnococcus granulosus protoscoleces infection in BALB/c mice[J]. PLoS One, 2013, 8(3): e59746.
[9]	Yu AP, Yin JH, Gong WC, et al. Changes of myeloid-derived suppressor cells and Th17 cells in mice infected with Echinococcus granulosus protoscoleces[J]. Chin J Parasitol Parasit Dis, 2018, 36(3): 224-230. (in Chinese)
	(于爱萍, 尹建海, 巩文词, 等. 细粒棘球蚴感染小鼠髓源抑制性细胞与Th17细胞比例的变化[J]. 中国寄生虫学与寄生虫病杂志, 2018, 36(3): 224-230.)
[10]	Veglia F, Sanseviero E, Gabrilovich DI. Myeloid-derived suppressor cells in the era of increasing myeloid cell diversity[J]. Nat Rev Immunol, 2021, 21(8): 485-498. doi: 10.1038/s41577-020-00490-y pmid: 33526920
[11]	Jou E, Rodriguez-Rodriguez N, Ferreira AF, et al. An innate IL-25-ILC2-MDSC axis creates a cancer-permissive microenvironment for Apc mutation-driven intestinal tumorigenesis[J]. Sci Immunol, 2022, 7(72): eabn0175.
[12]	Groth C, Hu XY, Weber R, et al. Immunosuppression mediated by myeloid-derived suppressor cells (MDSCs) during tumour progression[J]. Br J Cancer, 2019, 120(1): 16-25.
[13]	Özkan B, Lim H, Park SG. Immunomodulatory function of myeloid-derived suppressor cells during B cell-mediated immune responses[J]. Int J Mol Sci, 2018, 19(5): 1468.
[14]	Ma TM, Renz BW, Ilmer M, et al. Myeloid-derived suppressor cells in solid tumors[J]. Cells, 2022, 11(2): 310.
[15]	Condamine T, Ramachandran I, Youn JI, et al. Regulation of tumor metastasis by myeloid-derived suppressor cells[J]. Annu Rev Med, 2015, 66: 97-110. doi: 10.1146/annurev-med-051013-052304 pmid: 25341012
[16]	Safarzadeh E, Orangi M, Mohammadi H, et al. Myeloid-derived suppressor cells: important contributors to tumor progression and metastasis[J]. J Cell Physiol, 2018, 233(4): 3024-3036. doi: 10.1002/jcp.26075 pmid: 28661031
[17]	Cao SK, Pan W, Liu H, et al. Expression and activity of arginase from monocytic-type myeloid-derived suppressor cells in rats infected with Echinococcus granulosus[J]. Chin J Parasitol Parasit Dis, 2016, 34(1): 27-31. (in Chinese)
	(曹胜魁, 潘伟, 刘华, 等. 细粒棘球蚴感染小鼠单核髓源抑制性细胞精氨酸酶的表达和活性研究[J]. 中国寄生虫学与寄生虫病杂志, 2016, 34(1): 27-31.)
[18]	Zhang N, Zhang CS, Li ZD, et al. The effects of Echinococcus multilocularis protoscoleces infection on lymphocytes and their subpopulations in mouse liver and spleen[J]. Chin J Parasitol Parasit Dis, 2020, 38(1): 30-35. (in Chinese)
	(章宁, 张传山, 李智德, 等. 多房棘球蚴感染对小鼠肝脾淋巴细胞及其亚群的影响[J]. 中国寄生虫学与寄生虫病杂志, 2020, 38(1): 30-35.) doi: 10.12140/j.issn.1000-7423.2020.01.005
[19]	Zhang XF, Gong WC, Cao SK, et al. Dynamic changes of myeloid-derived suppressor cells and regulatory T cells in livers of mice infected with Echinococcus granulosus[J]. Chin J Schisto Control, 2019, 31(6): 622-627. (in Chinese)
	(张小凡, 巩文词, 曹胜魁, 等. 细粒棘球绦虫感染小鼠肝脏髓源抑制性细胞与调节性T细胞比例动态变化[J]. 中国血吸虫病防治杂志, 2019, 31(6): 622-627.)
[20]	Weber R, Riester Z, Hüser L, et al. IL-6 regulates CCR5 expression and immunosuppressive capacity of MDSC in murine melanoma[J]. J Immunother Cancer, 2020, 8(2): e000949.
[21]	Weber R, Groth C, Lasser S, et al. IL-6 as a major regulator of MDSC activity and possible target for cancer immunotherapy[J]. Cell Immunol, 2021, 359: 104254.
[22]	Grover A, Sanseviero E, Timosenko E, et al. Myeloid-derived suppressor cells: a propitious road to clinic[J]. Cancer Discov, 2021, 11(11): 2693-2706. doi: 10.1158/2159-8290.CD-21-0764 pmid: 34635571
[23]	Petrova V, Groth C, Bitsch R, et al. Immunosuppressive capacity of circulating MDSC predicts response to immune checkpoint inhibitors in melanoma patients[J]. Front Immunol, 2023, 14: 1065767.