Functional Inhibition of Natural Killer Cells in a BALB/c Mouse Model of Liver Fibrosis Induced by Schistosoma japonicum Infection.
Functional Inhibition of Natural Killer Cells in a BALB/c Mouse Model of Liver Fibrosis Induced by Schistosoma japonicum Infection.
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日本血吸虫感染诱导的 BALB/c 小鼠肝纤维化模型中自然杀伤细胞的功能抑制
DOI：
10.3389/fcimb.2020.598987
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发表时间：
2020
影响因子：
5.7
通讯作者：
Cao J
中科院分区：
文献类型：
--
作者：
Hu Y;Wang X;Wei Y;Liu H;Zhang J;Shen Y;Cao J
背景与目的日本血吸虫病是一种分布广泛的人兽共患疾病，我国血吸虫病患者肝纤维化发病率较高。许多研究表明，自然杀伤（NK）细胞可以通过直接杀伤肝星状细胞（HSC）来减缓肝纤维化的进展。但NK细胞不能抑制日本血吸虫感染诱导的肝纤维化进程。目的探讨NK细胞在血吸虫病中的作用。方法用S.日本尾蚴用流式细胞术检测感染小鼠肝、脾NK细胞上的受体及其比例。实时荧光定量PCR检测NK细胞IFN-γ、穿孔素、颗粒酶及肝组织Ⅰ、Ⅲ型胶原和α-SMA的表达。使用流式细胞仪珠阵列检测血清中细胞因子水平的变化。采用苏木精-伊红和Masson染色评价肝纤维化。分析血吸虫病模型NK细胞功能。结果感染后2 ~ 4周，NK细胞被激活，IFN-γ、穿孔素和颗粒酶等效应分子水平显著升高，并在感染后4周达到高峰。感染后6 ~ 10周，肝脏和脾脏中NK细胞的比例增加。然而，NK细胞的功能在感染后6至10周被抑制，活化受体（AR）、抑制性受体（IR）和效应分子的水平显著降低。小鼠血清中IFN-γ、IL-12和IL-6水平在感染后6周达到峰值，IL-10和IL-21水平在感染后8周达到峰值。肝纤维化指标在感染后6周显著升高。结论NK细胞在感染后2 ~ 4周被激活，参与了小鼠的炎症反应。在S.当日本血吸虫产卵时，NK细胞受到抑制，活化和抑制NK细胞受体以及细胞毒性分子的水平降低。此外，肝纤维化形成。感染S.结论：日本血吸虫对肝纤维化的抑制作用可能与解除NK细胞的功能抑制有关。
Background and Aims Schistosomiasis japonica is a widespread human zoonotic disease, and in China, there are many patients with schistosomiasis suffering from liver fibrosis. Many studies have shown that natural killer (NK) cells could reduce the progression of hepatic fibrosis by directly killing hepatic stellate cells (HSCs). However, NK cells could not inhibit the progress of liver fibrosis induced by Schistosoma japonicum infection. We aimed to investigate the function of NK cells in schistosomiasis. Methods BALB/c mice were infected with S. japonicum cercariae. The receptors and their proportions expressed on NK cells in the liver and spleen from infected mice were detected using flow cytometry. Levels of IFN-γ, perforin, and granzyme of NK cells, and collagen I, III, and α-SMA of hepatic tissue, were detected using quantitative real-time PCR. Changes in cytokine levels in sera were detected using a cytometric bead array. Liver fibrosis was evaluated using hematoxylin and eosin and Masson staining. NK function in the schistosomiasis model was analyzed. Results From 2 to 4 weeks post-infection, NK cells were activated, with significantly increased levels of effector molecules (IFN-γ, perforin, and granzyme) that peaked at 4 weeks after infection. The proportion of NK cells increased in the liver and spleen from 6 to 10 weeks post-infection. However, the function of NK cells was inhibited from 6 to 10 weeks post-infection with significantly decreased levels of activated receptors (AR), inhibitory receptors (IR), and effector molecules. The levels of IFN-γ, IL-12, and IL-6 in mouse serum peaked at 6 weeks post-infection, and IL-10 and IL-21 levels peaked at 8 weeks post-infection. Hepatic fibrosis markers increased significantly at 6 weeks after infection. Conclusion Our study suggested that NK cells were activated from 2 to 4 weeks post-infection and participated in inflammation in the mouse model. After the S. japonicum laid their eggs, NK cells became inhibited, with decreased levels of both activating and inhibitory NK cell receptors, as well as cytotoxic molecules. In addition, liver fibrosis formed. In mice infected with S. japonicum, the process of liver fibrosis might be alleviated by removing the functional inhibition of NK cells.
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影响因子：
2
作者：
Cha, Hefei;Qin, Wenjuan;Huang, Jun
通讯作者：
Huang, Jun
影响因子：
4.1
作者：
Liu P;Chen L;Zhang H
通讯作者：
Zhang H
自然杀伤细胞对日本血吸虫虫卵所致肝纤维化的负调控
影响因子：
3.8
作者：
Hou X;Yu F;Man S;Huang D;Zhang Y;Liu M;Ren C;Shen J
通讯作者：
Shen J
影响因子：
13.5
作者：
Kong, Xiaoni;Feng, Dechun;Wang, Hua;Hong, Feng;Bertola, Adeline;Wang, Fu-Sheng;Gao, Bin
通讯作者：
Gao, Bin
影响因子：
7.3
作者：
Fasbender F;Widera A;Hengstler JG;Watzl C
通讯作者：
Watzl C