ORIGINAL ARTICLES

Immunological characteristics of splenic dendritic cells subsets in mice at different stages of Echinococcus multilocularis infection

  • TANG Na ,
  • AYINAER Jiensi ,
  • XIAO Wenying ,
  • ABIDAN Ainiwaer ,
  • SUN Sheng ,
  • GE Conghui ,
  • WANG Mengying ,
  • GAO Yi ,
  • HU Qiu ,
  • LI Jing ,
  • ZHANG Chuanshan ,
  • WANG Hui
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  • 1 Basic Medical College, Xinjiang Medical University, Urumqi 830017, Xinjiang, China
    2 Institute of Clinical Medicine, The First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, Xinjiang, China

Received date: 2025-12-03

  Revised date: 2026-02-04

  Online published: 2026-04-27

Supported by

Young Top Talents Program of “Tianshan Talents” Training Plan in Xinjiang Uygur Autonomous Region(2024TSYCCX0102);Young Top Talents Program of “Tianshan Talents” Training Plan in Xinjiang Uygur Autonomous Region(2022TSYCCX0106);National Key Research and Development Program of China(2023YFD1801202);National Natural Science Foundation of China(82160397);National Natural Science Foundation of China(82372279);Natural Science Foundation of Xinjiang Uygur Autonomous Region(2025D01E36);Natural Science Foundation of Xinjiang Uygur Autonomous Region(2022D01D60)

Abstract

Objective To investigate the changes in the number, proportion and immunological characteristics of splenic dendritic cells (DCs) and their subsets in mice at different stages of Echinococcus multilocularis infection. Methods C57BL/6J mice were randomly divided into a control group and an infection group. Mice in the infection group were injected with 4 000 E. multilocularis protoscoleces via the hepatic portal vein, while mice in the control group received an equal volume of normal saline. Spleen tissues were collected at 2 weeks and 24 weeks post-infection, respectively. Paraffin-embedded sections were subjected to immunohistochemistry (IHC) to observe the localization of CD11c+ cells in spleen. Splenic lymphocytes were isolated, and flow cytometry was used to detect the number, proportion and expression of co-stimulatory molecules CD40 and CD80 on DCs and their subsets in the spleen of both groups. Results IHC results showed that CD11c+ cells in both the control and infection groups were predominantly localized in the marginal zone of the splenic white pulp at all infection stages, with no statistically significant difference in the proportion of positive staining area between groups (t = 0.473, -1.885; both P > 0.05). Flow cytometry revealed that at 2 and 24 weeks post-infection, splenic DCs in the infection group accounted for (11.33 ± 2.67)% and (15.24 ± 3.63)% of total splenic lymphocytes, respectively, both significantly lower than those in the control group [(18.08 ± 3.47)% and (22.06 ± 4.58)%, respectively] (t = 3.449, 2.761; P < 0.01, 0.05). The proportion of plasmacytoid DCs (pDCs) among splenic DCs was (11.41 ± 3.82)% in the control group and (9.71 ± 3.22)% in the infection group at 2 weeks post-infection, and (4.26 ± 1.59)% and (4.85 ± 1.16)%, respectively, at 24 weeks post-infection, with no statistically significant differences (t = 0.760, -0.707; both P > 0.05). The proportion of conventional DCs (cDCs) among splenic DCs was (52.38 ± 5.13)% in the control group and (35.96 ± 4.31)% in the infection group at 2 weeks post-infection, with the infection group significantly lower than the control group (t = 5.479, P < 0.01); at 24 weeks post-infection, the proportions were (30.46 ± 5.44)% and (32.18 ± 3.22)%, respectively, with no statistically significant difference (t = -0.654, P > 0.05). Among splenic cDCs, the proportion of CD103+CD11b- cells in the infection group was (14.24 ± 2.29)% at 2 weeks and (7.97 ± 1.75)% at 24 weeks post-infection, both significantly higher than those in the control group [(8.63 ± 0.60)% and (4.50 ± 1.28)%, respectively] (t = -5.294, -3.681; both P < 0.01). The proportion of CD103-CD11b+ cells among splenic cDCs in the infection group was (45.74 ± 4.43)% at 2 weeks post-infection, significantly higher than that in the control group [(38.12 ± 4.58)%] (t = -2.672, P < 0.05), but was (50.42 ± 6.97)% at 24 weeks post-infection, significantly lower than that in the control group [(59.06 ± 4.51)%] (t = 2.378, P < 0.05). At 2 weeks post-infection, the proportions of CD40+ cells among splenic DCs, pDCs, and cDCs in the infection group were (13.89 ± 2.96)%, (2.33 ± 0.64)%, and (11.10 ± 1.93)%, respectively, all significantly lower than those in the control group [(23.98 ± 2.94)%, (3.75 ± 0.93)%, and (20.22 ± 2.84)%, respectively] (t = 5.412, 2.818, 5.943; P < 0.01, 0.05, 0.01). At 2 weeks post-infection, the proportions of CD80+ cells among splenic DCs and cDCs in the infection group were (27.78 ± 11.22)% and (19.36 ± 9.64)%, respectively, both significantly lower than those in the control group [(44.16 ± 8.11)% and (33.42 ± 7.61)%, respectively] (t = 2.645, 2.559; both P < 0.05). At 24 weeks post-infection, the proportions of CD80+ cells among splenic DCs and cDCs in the infection group were (47.22 ± 2.42)% and (31.00 ± 2.56)%, respectively, both significantly higher than those in the control group [(29.26 ± 7.88)% and (20.30 ± 7.45)%, respectively] (t = -5.338, -3.321; both P < 0.01). Conclusion In the early stage of E. multilocularis infection, the number of splenic DCs and cDCs decreased, and the expression of CD40 and CD80 was down-regulated, suggesting impaired DC maturation. In the late stage of infection, the number of DCs and cDCs increased, and CD80 expression was up-regulated, reflecting the evolution of the immune response during the late phase of infection.

Cite this article

TANG Na , AYINAER Jiensi , XIAO Wenying , ABIDAN Ainiwaer , SUN Sheng , GE Conghui , WANG Mengying , GAO Yi , HU Qiu , LI Jing , ZHANG Chuanshan , WANG Hui . Immunological characteristics of splenic dendritic cells subsets in mice at different stages of Echinococcus multilocularis infection[J]. CHINESE JOURNAL OF PARASITOLOGY AND PARASITIC DISEASES, 2026 , 44(2) : 158 -165 . DOI: 10.12140/j.issn.1000-7423.2026.02.002

References

[1] Wen H, Vuitton L, Tuxun T, et al. Echinococcosis: advances in the 21st century[J]. Clin Microbiol Rev, 2019, 32(2): e00075-e00018.
[2] Reinehr M, Micheloud C, Grimm F, et al. Pathology of echinococcosis: a morphologic and immunohistochemical study on 138 specimens with focus on the differential diagnosis between cystic and alveolar echinococcosis[J]. Am J Surg Pathol, 2020, 44(1): 43-54.
[3] Casulli A, Barth TFE, Tamarozzi F. Echinococcus multilocularis[J]. Trends Parasitol, 2019, 35(9): 738-739.
[4] Kui Y, Han S, Zhang XJ, et al. Analysis of epidemiological and issues encountered in case reports on echinococcosis - China, 2022[J]. China CDC Wkly, 2024, 6(6): 100-104.
[5] 刘白雪, 蒉嫣, 薛垂召, 等. 2023年全国棘球蚴病防治工作进展[J]. 中国寄生虫学与寄生虫病杂志, 2025, 43(1): 8-16.
  Liu BX, Kui Y, Xue CZ, et al. Progress of the national echinococcosis control programme in China, 2023[J]. Chin J Parasitol Parasit Dis, 2025, 43(1): 8-16. (in Chinese)
[6] 孙备, 李承. 脾脏功能的研究进展[J]. 临床外科杂志, 2006, 14(7): 450-452.
  Sun B, Li C. Research progress on spleen function[J]. J Clin Surg, 2006, 14(7): 450-452. (in Chinese)
[7] 杨春青, 王琴琴, 辛青, 等. 脾脏巨噬细胞与树突状细胞相互作用机制的研究进展[J]. 细胞与分子免疫学杂志, 2019, 35(8): 762-766.
  Yang CQ, Wang QQ, Xin Q, et al. Research progress on the interaction mechanism between splenic macrophages and dendritic cells[J]. Chin J Cell Mol Immunol, 2019, 35(8): 762-766. (in Chinese)
[8] Shi Q, Zhuang F, Liu JT, et al. Single-cell analyses reveal functional classification of dendritic cells and their potential roles in inflammatory disease[J]. FASEB J, 2019, 33(3): 3784-3794.
[9] Nutt SL, Chopin M. Transcriptional networks driving dendritic cell differentiation and function[J]. Immunity, 2020, 52(6): 942-956.
[10] Bruno L. Differentiation of dendritic cell subsets from mouse bone marrow[M]// Immunological Tolerance. Totowa, NJ: Humana Press, 2007: 47-57.
[11] He ZM, Zhu XY, Shi Z, et al. Metabolic regulation of dendritic cell differentiation[J]. Front Immunol, 2019, 10: 410.
[12] Jiménez-Cortegana C, Palomares F, Alba G, et al. Dendritic cells: the Yin and Yang in disease progression[J]. Front Immunol, 2024, 14: 1321051.
[13] Amon L, Lehmann CHK, Baranska A, et al. Transcriptional control of dendritic cell development and functions[M]// Immunobiology of Dendritic Cells Part B. Amsterdam: Elsevier, 2019: 55-151.
[14] 曲凯歌, 赵权, 姜晶, 等. 树突状细胞在寄生虫感染免疫中的作用[J]. 中国寄生虫学与寄生虫病杂志, 2014, 32(2): 152-156.
  Qu KG, Zhao Q, Jiang J, et al. Immunity to parasitic infection: the role of dendritic cells[J]. Chin J Parasitol Parasit Dis, 2014, 32(2): 152-156. (in Chinese)
[15] Steinman RM, Hawiger D, Nussenzweig MC. Tolerogenic dendritic cells[J]. Annu Rev Immunol, 2003, 21: 685-711.
[16] Pan J, Jiang Z, Wu D, et al. Huaier extractum promotes dendritic cells maturation and favors them to induce Th1 immune response: one of the mechanisms underlying its anti-tumor activity[J]. Integr Cancer Ther, 2020, 19: 1534735420946830.
[17] Yuan XH, Yang XJ, Han CX. Regulation of dendritic cell immune function and maturation by the recombinant antigen p53 of Trichinella spiralis[J]. Parasites Vectors, 2025, 18(1): 423.[LinkOut]
[18] Wang H, Li Y, Yu Q, et al. Immunological characteristics of hepatic dendritic cells in patients and mouse model with liver Echinococcus multilocularis infection[J]. Trop Med Infect Dis, 2024, 9(5): 1-14.
[19] Wang H, Li J, Guo BP, et al. In vitro culture of Echinococcus multilocularis producing protoscoleces and mouse infection with the cultured vesicles[J]. Parasites Vectors, 2016, 9(1): 411.
[20] Zhang CS, Shao YM, Yang ST, et al. T-cell tolerance and exhaustion in the clearance of Echinococcus multilocularis: role of inoculum size in a quantitative hepatic experimental model[J]. Sci Rep, 2017, 7: 11153.
[21] 李玲慧, 王伟, 侯昕伶, 等. 多房棘球蚴感染对小鼠脾自然杀伤T细胞及其亚群的影响[J]. 中国寄生虫学与寄生虫病杂志, 2021, 39(3): 311-317.
  Li LH, Wang W, Hou XL, et al. Affects of Echinococcus multilocularis metacestode infection on the natural killer T cells and their subsets in mouse spleen[J]. Chin J Parasitol Parasit Dis, 2021, 39(3): 311-317. (in Chinese)
[22] Rahman AH, Aloman C. Dendritic cells and liver fibrosis[J]. Biochim Biophys Acta, 2013, 1832(7): 998-1004.
[23] Zhou Q, Gao J, Wu GR, et al. Adipose progenitor cell-derived extracellular vesicles suppress macrophage M1 program to alleviate midlife obesity[J]. Nat Commun, 2025, 16: 2743.
[24] Krueger PD, Kim TS, Sung SJ, et al. Liver-resident CD103+ dendritic cells prime antiviral CD8+ T cells in situ[J]. J Immunol, 2015, 194(7): 3213-3222.
[25] Hurdayal R, Nieuwenhuizen NE, Khutlang R, et al. Inflammatory dendritic cells, regulated by IL-4 receptor alpha signaling, control replication, and dissemination of Leishmania major in mice[J]. Front Cell Infect Microbiol, 2020, 9: 479.
[26] Meinderts SM, Oldenborg PA, Beuger BM, et al. Human and murine splenic neutrophils are potent phagocytes of IgG-opsonized red blood cells[J]. Blood Adv, 2017, 1(14): 875-886.
[27] Weng XD, Mu ZQ, Wei X, et al. Correction to: the effects of dog management on Echinococcus spp. prevalence in villages on the eastern Tibetan Plateau, China[J]. Parasit Vectors, 2021, 14(1): 124.
[28] Jenne CN, Kubes P. Immune surveillance by the liver[J]. Nat Immunol, 2013, 14(10): 996-1006.
[29] Musumeci A, Lutz K, Winheim E, et al. What makes a pDC: recent advances in understanding plasmacytoid DC development and heterogeneity[J]. Front Immunol, 2019, 10: 1222.
[30] 侯昕伶, 李玲慧, 李亮, 等. 多房棘球蚴感染小鼠脾CD4+T细胞亚群及其功能耗竭的变化[J]. 中国寄生虫学与寄生虫病杂志, 2020, 38(5): 611-618, 624.
  Hou XL, Li LH, Li L, et al. Changes in subsets and functional exhaustion of CD4+T cells in spleens of mice infected with Echinococcus multilocularis[J]. Chin J Parasitol Parasit Dis, 2020, 38(5): 611-618, 624. (in Chinese)
[31] 侯昕伶, 李亮, 李玲慧, 等. 泡球蚴感染对小鼠脾脏CD8+T细胞免疫功能耗竭的影响[J]. 中国血吸虫病防治杂志, 2020, 32(6): 591-597, 604.
  Hou XL, Li L, Li LH, et al. Exhaustion of CD8+T cell immune functions in spleen of mice with different doses of Echinococcus multilocularis infections[J]. Chin J Schisto Control, 2020, 32(6): 591-597, 604. (in Chinese)
[32] 侯娇, 温浩, 王明坤, 等. 多房棘球蚴感染小鼠脾脏巨噬细胞亚群及其极化表型的变化[J]. 中国寄生虫学与寄生虫病杂志, 2021, 39(6): 771-778.
  Hou J, Wen H, Wang MK, et al. Changes of macrophage subsets and polarization in spleen of mice infected with Echinococcus multilocularis[J]. Chin J Parasitol Parasit Dis, 2021, 39(6): 771-778. (in Chinese)
[33] Oshi M, Newman S, Tokumaru Y, et al. Plasmacytoid dendritic cell (pDC) infiltration correlate with tumor infiltrating lymphocytes, cancer immunity, and better survival in triple negative breast cancer (TNBC) more strongly than conventional dendritic cell (cDC)[J]. Cancers, 2020, 12(11): 3342.
[34] 石大林, 庞明泉, 毋德芳, 等. 肝多房棘球蚴病免疫微环境异质性及其对疾病进展的影响[J]. 中国寄生虫学与寄生虫病杂志, 2025, 43(4): 581-587, 591.
  Shi DL, Pang MQ, Wu DF, et al. Heterogeneity of the immune microenvironment in hepatic alveolar echinococcosis and its impact on disease progression[J]. Chin J Parasitol Parasit Dis, 2025, 43(4): 581-587, 591. (in Chinese)
[35] 刘茜, 吕艺, 陆江阳. MODS小鼠病程不同阶段脾脏树突状细胞免疫活性变化特征[J]. 中国免疫学杂志, 2014, 30(2): 167-172.
  Liu Q, LüY, Lu JY. Features of changes in splenic dendritic cell immunoactivity during progression of MODS in zymosan-challenged mice[J]. Chin J Immunol, 2014, 30(2): 167-172. (in Chinese)
[36] Nono JK, Pletinckx K, Lutz MB, et al. Excretory/secretory-products of Echinococcus multilocularis larvae induce apoptosis and tolerogenic properties in dendritic cells in vitro[J]. PLoS Negl Trop Dis, 2012, 6(2): e1516.
[37] Jenne L, Arrighi JF, Sauter B, et al. Dendritic cells pulsed with unfractionated helminthic proteins to generate antiparasitic cytotoxic T lymphocyte[J]. Parasite Immunol, 2001, 23(4): 195-201.
[38] Mejri N, Müller N, Hemphill A, et al. Intraperitoneal Echinococcus multilocularis infection in mice modulates peritoneal CD4+ and CD8+ regulatory T cell development[J]. Parasitol Int, 2011, 60(1): 45-53.
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