Department of Clinical Laboratory, Tumor Hospital Affiliated to Xinjiang Medical University, 830011, Urumqi, China.
Reproductive Medicine Center, First Affiliated Hospital of Xinjiang Medical University, 830011, Urumqi, Xinjiang, China.
Mol Biol Rep. 2022 Aug;49(8):7497-7506. doi: 10.1007/s11033-022-07554-3. Epub 2022 Jun 17.
Tim-3/Galectin-9 is involved in the immune escape of many pathogens. However, the role of Tim-3/Galectin-9 in persistent infection of Echinococcus multilocularis (Em), which is related to immune escape, is still unclear.
To investigate the role of Tim-3/Galectin-9 and related cytokines in mice with persistent infection of Em.
Em infection model was established by injecting the protoscoleces. Serum was collected at days 2, 8, 30, 60, 90, 180 and 270 after infection. Lymphocytes were isolated from liver tissue samples with Ficoll. Tim-3 + CD4 + T percentage was analyzed by flow cytometry. CD4 + T cells were isolated from liver tissues of Em infected mice and cultured in vitro. The mRNA levels of Tim-3, Galectin-9, IFN-γ and IL-4 were detected by qRT-PCR. Cytokine levels in serum and culture supernatant (IFN-γ and IL-4) were analyzed by cytometric bead array.
The expression of Tim-3 and Galectin-9 mRNA significantly increased after 30 days of infection, reached peak on day 90, and then decreased slightly on days 180-270. The expression of IFN-γ mRNA, increased on day 2 and 8 after infection, slightly decreased on days 30-60, and obvious decreased on days 90-270, but were still higher than those of the control group. The expression of IL-4 mRNA gradually increased along with the time of infection. In serum of Em infected mice, level of IFN-γ peaked at day 30 and then gradually decreased; whereas IL-4 level peaked at day 90 and then gradually decreased. In vitro experiment found that Tim-3/Galectin-9 directly caused the changes in the levels of IFN-γ and IL-4.
Tim-3/Galectin-9 signaling pathway may be involved in the development of persistent infection of Em by regulating the production of Th1 and Th2 cytokines.
Tim-3/Galectin-9 参与了许多病原体的免疫逃逸。然而，Tim-3/Galectin-9 在与免疫逃逸相关的多房棘球蚴（Em）持续感染中的作用尚不清楚。
探讨 Tim-3/Galectin-9 及相关细胞因子在 Em 持续感染小鼠中的作用。
通过注射原头蚴建立 Em 感染模型。分别于感染后第 2、8、30、60、90、180 和 270 天收集血清。采用 Ficoll 从肝组织样本中分离淋巴细胞。采用流式细胞术分析 Tim-3+CD4+T 细胞的百分比。从 Em 感染小鼠的肝组织中分离 CD4+T 细胞并在体外培养。采用 qRT-PCR 检测 Tim-3、Galectin-9、IFN-γ 和 IL-4 的 mRNA 水平。采用细胞因子微珠阵列分析血清和培养上清液（IFN-γ 和 IL-4）中的细胞因子水平。
感染 30 天后 Tim-3 和 Galectin-9 mRNA 的表达明显增加，第 90 天达到峰值，随后在 180-270 天略有下降。IFN-γ mRNA 的表达在感染后第 2 和 8 天增加，在 30-60 天略有下降，在 90-270 天明显下降，但仍高于对照组。IL-4 mRNA 的表达随着感染时间的延长而逐渐增加。Em 感染小鼠血清中 IFN-γ 水平在第 30 天达到峰值，随后逐渐下降；而 IL-4 水平在第 90 天达到峰值，随后逐渐下降。体外实验发现，Tim-3/Galectin-9 直接导致 IFN-γ 和 IL-4 水平的变化。
Tim-3/Galectin-9 信号通路可能通过调节 Th1 和 Th2 细胞因子的产生，参与 Em 的持续感染。
