多房棘球蚴感染小鼠脾1型先天淋巴细胞亚群及其相关因子表达变化

doi:10.12140/j.issn.1000-7423.2026.02.003

中国寄生虫学与寄生虫病杂志 ›› 2026, Vol. 44 ›› Issue (2): 166-173.doi: 10.12140/j.issn.1000-7423.2026.02.003

多房棘球蚴感染小鼠脾1型先天淋巴细胞亚群及其相关因子表达变化

肖雯颖¹(), 阿比旦·艾尼瓦尔¹, 葛聪蕙¹, 唐娜¹, 孙胜¹, 王梦颖¹, 高毅¹, 阿依娜尔·吉恩斯¹, 胡秋¹, 李静¹^,², 王慧¹^,³, 张传山¹^,³^,^*()()

¹ 新疆医科大学基础医学院，新疆乌鲁木齐 830017
² 新疆维吾尔自治区地方病分子生物学重点实验室，新疆乌鲁木齐 830054
³ 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:2025-11-04 修回日期:2026-02-27 出版日期:2026-04-30 发布日期:2026-04-28
通讯作者: * 张传山（ORCID：0000-0002-3241-2224），男，博士，研究员，从事寄生虫感染与免疫研究。E-mail：dashan0518@126.com
作者简介:肖雯颖，女，硕士研究生，从事寄生虫感染与免疫研究。E-mail：1718272894@qq.com
作者贡献
肖雯颖、阿比旦•艾尼瓦尔、唐娜、孙胜负责流式细胞术检测和分析；葛聪蕙、王梦颖、高毅、阿依娜尔•吉恩斯、胡秋负责多房棘球蚴保种、动物模型建立和动物组织采集；张传山、王慧、李静、肖雯颖负责课题设计和论文撰写及修改。
基金资助:
新疆维吾尔自治区自然科学基金(2022D01D60);国家自然科学基金(82372279);国家自然科学基金(82160396);国家重点研发计划项目(2023YFD1801202);新疆维吾尔自治区天山创新团队计划(2024D14010);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);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);国家级科研创新人才及科研创新团队培育项目(XYD2024GR01)

Changes of splenic type 1 innate lymphoid cells subsets and their related factors expression in mice infected with Echinococcus multilocularis

XIAO Wenying¹(), ABIDAN Ainiwaer¹, GE Conghui¹, TANG Na¹, SUN Sheng¹, WANG Mengying¹, GAO Yi¹, AYINAER Jiensi¹, HU Qiu¹, LI Jing¹^,², WANG Hui¹^,³, ZHANG Chuanshan¹^,³^,^*()()

¹ College of Basic Medical, Xinjiang Medical University, Urumqi 830017, Xinjiang, China
² Xinjiang Uygur Autonomous Region Key Laboratory of Molecular Biology for Endemic Diseases, Urumqi 830054, Xinjiang, China
³ Institute of Clinical Medicine, The First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, Xinjiang, China

Received:2025-11-04 Revised:2026-02-27 Online:2026-04-30 Published:2026-04-28
Supported by:
Natural Science Foundation of Xinjiang Uygur Autonomous Region(2022D01D60);National Natural Science Foundation of China(82372279);National Natural Science Foundation of China(82160396);National Key Research and Development Program(2023YFD1801202);Xinjiang Uygur Autonomous Region Tianshan Innovation Team Program(2024D14010);Xinjiang Uygur Autonomous Region “Tianshan Talent” Cultivation Program for Young Top-notch Talents(2022TSYCCX0106);Xinjiang Uygur Autonomous Region “Tianshan Talent” Cultivation Program for Young Top-notch Talents(2024TSYCCX0102);National Program for Cultivating Scientific Research Innovation Talents and Teams(XYD2024GR01)

摘要/Abstract

摘要：

目的探讨多房棘球蚴感染对小鼠脾脏1型先天淋巴细胞（ILC1）亚群及其相关因子表达水平的影响。方法将C57BL/6J小鼠随机分为对照组和感染组，感染组小鼠经门静脉注射3 000个原头节，对照组小鼠注射相同体积的生理盐水。感染24周后，取小鼠脾组织制备石蜡切片，采用苏木素-伊红（HE）染色法观察小鼠脾脏病理变化。提取小鼠脾淋巴细胞，采用流式细胞术检测脾ILC1亚群数量和分化状态、免疫检查点受体表达和细胞因子分泌水平。结果 HE染色显示，感染组小鼠脾组织红髓与白髓边缘区模糊，白髓区产生铁血素沉积。流式细胞术检测结果显示，对照组小鼠脾自然杀伤（NK）细胞占脾淋巴细胞总数的（2.52 ± 0.44）%，高于感染组的（1.25 ± 0.28）%（t = 6.42，P < 0.01）；对照组小鼠脾ILC1占脾NK细胞的（20.07 ± 2.70）%，低于感染组的（31.49 ± 3.28）%（t = 7.10，P < 0.01）；感染组小鼠脾常规NK（cNK）细胞占脾NK细胞的（68.89 ± 3.28）%，低于对照组的（80.14 ± 3.49）%（t = 6.22，P < 0.01）。感染组小鼠脾ILC1中CD27^-CD11b⁺细胞占（21.37 ± 7.48）%，低于对照组的（43.49 ± 8.05）%（t = 5.33，P < 0.01）；CD27⁺CD11b^-和CD27⁺CD11b⁺细胞分别占（39.64 ± 8.80）%和（6.77 ± 1.51）%，高于对照组的（24.51 ± 8.35）%和（4.12 ± 1.71）%（t = 3.30、3.06，均P < 0.01）。感染组小鼠脾ILC1中分泌程序性死亡受体1（PD-1）和糖皮质激素诱导的肿瘤坏死因子受体（GITR）的细胞分别占（5.04 ± 1.54）%和（16.14 ± 4.53）%，高于对照组的（2.57 ± 1.52）%和（10.81 ± 4.03）%（t = 3.02、2.33，均P < 0.05）；分泌颗粒酶B（Gr-B）和γ干扰素（IFN-γ）的细胞分别占（6.16 ± 1.23）%和（16.13 ± 6.64）%，低于对照组的（9.42 ± 2.16）%和（30.68 ± 6.81）%（t = 2.94、3.42，P < 0.05、0.01）；分泌肿瘤坏死因子α（TNF-α）的细胞占（22.26 ± 6.69）%，高于对照组的（10.80 ± 3.92）%（t = 3.31，P < 0.05）。结论多房棘球蚴感染晚期，小鼠脾脏ILC1比例及未成熟ILC1比例增加，抑制性免疫检查点受体PD-1高表达，分泌细胞因子Gr-B和IFN-γ的能力下降，提示ILC1功能抑制可能促进了多房棘球蚴的慢性感染。

关键词: 多房棘球蚴, 多房棘球蚴病, 脾脏, NK细胞, ILC1, 免疫检查点受体

Abstract:

Objective To investigate the effects of Echinococcus multilocularis infection on the proportion of type 1 innate lymphoid cells (ILC1) and the expression levels of related factors in the spleen of mice. Methods C57BL/6J mice were randomly divided into the control group and the infection group. The infection group mice were injected with 3 000 E. multilocularis protoscoleces via the portal vein, while the control group mice were injected with the same volume of normal saline. After 24 weeks, spleen tissue sections were prepared from the infection group and the control group mice, and hematoxylin-eosin (HE) staining was used to observe the pathological changes in the spleen. Splenic lymphocytes were isolated from the mice, and flow cytometry was used to detect the proportion of ILC1 cell subsets, the expression of immune checkpoint molecules, and the levels of secreted cytokines in the spleen. Results HE staining showed that the boundary between the red pulp and the marginal zone of the white pulp was blurred in the spleen of mice infected with E. multilocularis, and hemosiderin deposition occurred in the white pulp area. Flow cytometry results indicated that the percentage of splenic natural killer (NK) cells among total splenic lymphocytes in the control group was (2.52 ± 0.44)%, which was higher than that in the infection group (1.25 ± 0.28)% (t = 6.42，P < 0.01). The percentage of splenic ILC1 among splenic NK cells in the control group was (20.07 ± 2.70)%, which was lower than that in the infection group (31.49 ± 3.28)% (t = 7.10, P < 0.01). The percentage of splenic conventional NK (cNK) cells among splenic NK cells in the infection group was (68.89 ± 3.28)%, which was lower than that in the control group (80.14 ± 3.49)% (t = 6.22, P < 0.01). The percentage of CD27^-CD11b⁺ cells among splenic ILC1 in the infection group was (21.37 ± 7.48)%, which was lower than that in the control group (43.49 ± 8.05)% (t = 5.33, P < 0.01); the percentages of CD27⁺CD11b^- and CD27⁺CD11b⁺ cells were (39.64 ± 8.80)% and (6.77 ± 1.51)%, respectively, which were higher than those in the control group (24.51 ± 8.35)% and (4.12 ± 1.71)% (t = 3.30, 3.06; both P < 0.01). The percentages of splenic ILC1 secreting programmed death receptor 1 (PD-1) and glucocorticoid-induced tumor necrosis factor receptor (GITR) in the infection group were (5.04 ± 1.54)% and (16.14 ± 4.53)%, respectively, which were higher than those in the control group (2.57 ± 1.52)% and (10.81 ± 4.03)% (t = 3.02, 2.33; both P < 0.05). The percentages of splenic ILC1 secreting granzyme B (Gr-B) and interferon-γ (IFN-γ) in the infection group were (6.16 ± 1.23)% and (16.13 ± 6.64)%, respectively, which were lower than those in the control group (9.42 ± 2.16)% and (30.68 ± 6.81)% (t = 2.94, 3.42; P < 0.05, 0.01). The percentage of splenic ILC1 secreting tumor necrosis factor-α (TNF-α) in the infection group was (22.26 ± 6.69)%, which was higher than that in the control group (10.80 ± 3.92)% (t = 3.31, P < 0.05). Conclusion In the late stage of E. multilocularis infection, the proportion of ILC1 cells and immature ILC1 cells were increased in mouse spleen. The co-inhibitory immune checkpoint molecule PD-1 was highly expressed, and the ability of these cells to secrete cytokines Gr-B and IFN-γ decreased. This suggested that ILC1 cell function suppressed might promote the chronic parasitism of E. multilocularis.

Key words: Echinococcus multilocularis, Alveolar echinococcosis, Spleen, NK cells, ILC1, Immune checkpoint molecules

中图分类号:

R532.32

肖雯颖, 阿比旦·艾尼瓦尔, 葛聪蕙, 唐娜, 孙胜, 王梦颖, 高毅, 阿依娜尔·吉恩斯, 胡秋, 李静, 王慧, 张传山. 多房棘球蚴感染小鼠脾1型先天淋巴细胞亚群及其相关因子表达变化[J]. 中国寄生虫学与寄生虫病杂志, 2026, 44(2): 166-173.

XIAO Wenying, ABIDAN Ainiwaer, GE Conghui, TANG Na, SUN Sheng, WANG Mengying, GAO Yi, AYINAER Jiensi, HU Qiu, LI Jing, WANG Hui, ZHANG Chuanshan. Changes of splenic type 1 innate lymphoid cells subsets and their related factors expression in mice infected with Echinococcus multilocularis[J]. Chinese Journal of Parasitology and Parasitic Diseases, 2026, 44(2): 166-173.

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多房棘球蚴感染小鼠脾1型先天淋巴细胞亚群及其相关因子表达变化

Changes of splenic type 1 innate lymphoid cells subsets and their related factors expression in mice infected with Echinococcus multilocularis

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