小鼠感染多房棘球蚴不同阶段脾树突状细胞亚群免疫特征变化

doi:10.12140/j.issn.1000-7423.2026.02.002

中国寄生虫学与寄生虫病杂志 ›› 2026, Vol. 44 ›› Issue (2): 158-165.doi: 10.12140/j.issn.1000-7423.2026.02.002

小鼠感染多房棘球蚴不同阶段脾树突状细胞亚群免疫特征变化

唐娜¹^,²(), 阿依娜尔·吉恩斯¹^,², 肖雯颖¹^,², 阿比旦·艾尼瓦尔¹^,², 孙胜¹^,², 葛聪蕙¹^,², 王梦颖¹^,², 高毅¹^,², 胡秋¹^,², 李静¹, 张传山¹^,², 王慧¹^,²^,^*()()

¹ 新疆医科大学基础医学院，新疆乌鲁木齐 830017
² 新疆医科大学第一附属医院临床医学研究院，新疆乌鲁木齐 830054

收稿日期:2025-12-03 修回日期:2026-02-04 出版日期:2026-04-30 发布日期:2026-04-27
通讯作者: * 王慧（ORCID：0000-0002-9308-6186），女，博士，研究员，从事寄生虫感染与免疫研究。E-mail：wangh0923@126.com
作者简介:唐娜，女，硕士研究生，从事寄生虫感染与免疫研究。E-mail：tangna1020@126.com
作者贡献
唐娜、阿比旦·艾尼瓦尔、孙胜负责流式细胞术检测和分析；唐娜、阿依娜尔·吉恩斯、肖雯颖、葛聪蕙、王梦颖、高毅、胡秋负责多房棘球蚴保种、动物模型建立和动物组织采集；王慧、张传山、李静、唐娜负责课题设计和论文撰写修改。
基金资助:
新疆维吾尔自治区“天山英才”培养计划青年拔尖人才项目(2024TSYCCX0102);新疆维吾尔自治区“天山英才”培养计划青年拔尖人才项目(2022TSYCCX0106);国家重点研发计划项目(2023YFD1801202);国家自然科学基金(82160397);国家自然科学基金(82372279);新疆维吾尔自治区自然科学基金(2025D01E36);新疆维吾尔自治区自然科学基金(2022D01D60)

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

TANG Na¹^,²(), AYINAER Jiensi¹^,², XIAO Wenying¹^,², ABIDAN Ainiwaer¹^,², SUN Sheng¹^,², GE Conghui¹^,², WANG Mengying¹^,², GAO Yi¹^,², HU Qiu¹^,², LI Jing¹, ZHANG Chuanshan¹^,², WANG Hui¹^,²^,^*()()

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:2025-12-03 Revised:2026-02-04 Online:2026-04-30 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)

摘要/Abstract

摘要：

目的探讨多房棘球蚴感染小鼠不同阶段脾树突状细胞（DC）及其亚群的数量、比例和免疫特征变化。方法将C57BL/6J小鼠随机分为对照组和感染组，感染组小鼠经肝门静脉注射4 000个多房棘球蚴原头节，对照组小鼠注射等体积生理盐水，分别于感染后2周和24周采集小鼠脾组织，石蜡切片后进行免疫组织化学染色（IHC），观察CD11c阳性细胞在脾组织的定位。提取小鼠脾淋巴细胞，利用流式细胞术检测两组小鼠脾脏中DC及其亚群数量、比例和表面共刺激分子CD40和CD80的表达变化。结果 IHC结果显示，对照组和感染组小鼠脾CD11c阳性细胞在不同感染阶段均主要定位于脾脏白髓边缘区，区域占比的差异无统计学意义（t = 0.473、-1.885，均P > 0.05）。流式细胞术检测结果显示，感染后2周和24周，感染组小鼠脾DC分别占脾淋巴细胞总数的（11.33 ± 2.67）%和（15.24 ± 3.63）%，均低于对照组的（18.08 ± 3.47）%和（22.06 ± 4.58）%（t = 3.449、2.761，P < 0.01、0.05）。对照组和感染组小鼠脾浆细胞样DC（pDC）在感染后2周分别占脾DC的（11.41 ± 3.82）%和（9.71 ± 3.22）%，感染后24周分别占（4.26 ± 1.59）%和（4.85 ± 1.16）%，差异均无统计学意义（t = 0.760、-0.707，均P > 0.05）。对照组和感染组小鼠脾传统DC（cDC）在感染后2周分别占脾DC的（52.38 ± 5.13）%和（35.96 ± 4.31）%，感染组低于对照组（t = 5.479，P < 0.01）；在感染后24周分别占（30.46 ± 5.44）%和（32.18 ± 3.22）%，差异无统计学意义（t = -0.654，P > 0.05）。感染组小鼠脾cDC中CD103⁺CD11b^-细胞在感染后2周和24周分别占（14.24 ± 2.29）%和（7.97 ± 1.75）%，均高于对照组的（8.63 ± 0.60）%和（4.50 ± 1.28）%（t = -5.294、-3.681，均P < 0.01）；感染组小鼠脾cDC中CD103^-CD11b⁺细胞在感染后2周占（45.74 ± 4.43）%、高于对照组的（38.12 ± 4.58）%（t = -2.672，P < 0.05），在感染后24周占（50.42 ± 6.97）%、低于对照组的（59.06 ± 4.51）%（t = 2.378，P < 0.05）。感染后2周，感染组小鼠脾DC、pDC和cDC中CD40⁺细胞分别占（13.89 ± 2.96）%、（2.33 ± 0.64）%和（11.10 ± 1.93）%，均低于对照组的（23.98 ± 2.94）%、（3.75 ± 0.93）%和（20.22 ± 2.84）%（t = 5.412、2.818、5.943，P < 0.01、0.05、0.01）。感染后2周，感染组小鼠脾DC和cDC中CD80⁺细胞分别占（27.78 ± 11.22）%和（19.36 ± 9.64）%，均低于对照组的（44.16 ± 8.11）%和（33.42 ± 7.61）%（t = 2.645、2.559，均P < 0.05）；感染后24周，感染组小鼠脾DC和cDC中CD80⁺细胞分别占（47.22 ± 2.42）%和（31.00 ± 2.56）%，均高于对照组的（29.26 ± 7.88）%和（20.30 ± 7.45）%（t = -5.338、-3.321，均P < 0.01）。结论多房棘球蚴感染早期，小鼠脾DC和cDC数量减少，CD40和CD80表达下调，提示DC成熟受抑；感染晚期，DC与cDC数量增多，CD80表达增强，反映了感染后期免疫应答状态的演变。

关键词: 多房棘球蚴病, 多房棘球蚴, 脾脏, 树突状细胞, 共刺激分子

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.

Key words: Alveolar echinococcoisis, Echinococcus multilocularis, Spleen, Dendritic cell, Co-stimulatory molecules

中图分类号:

R532.32

唐娜, 阿依娜尔·吉恩斯, 肖雯颖, 阿比旦·艾尼瓦尔, 孙胜, 葛聪蕙, 王梦颖, 高毅, 胡秋, 李静, 张传山, 王慧. 小鼠感染多房棘球蚴不同阶段脾树突状细胞亚群免疫特征变化[J]. 中国寄生虫学与寄生虫病杂志, 2026, 44(2): 158-165.

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.

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小鼠感染多房棘球蚴不同阶段脾树突状细胞亚群免疫特征变化

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

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