National Reference Laboratory for Animal Schistosomiasis, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, 200241, P.R. China.
Key Laboratory of Animal Parasitology of Ministry of Agriculture, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, 200241, P.R. China.
Parasit Vectors. 2021 Oct 24;14(1):548. doi: 10.1186/s13071-021-05063-z.
Schistosomiasis japonica is a serious zoonotic parasitic disease. Preliminary studies have shown that the expression of microRNA-181a (miR-181a) in the liver, lung and spleen tissues of susceptible host BALB/c mice and resistant host reed vole (Microtus fortis) 10 days post-infection (dpi) with Schistosoma japonicum was significantly different from pre-infection levels. This difference suggests the possibility that miR-181a expression may be related to the regulation of the hosts' early immune response against S. japonicum infection and thereby affect the development and survival of parasites in their final hosts.
BALB/c mice, M. fortis, Toll-like receptor 4 (TLR4)-deficient mice and wild-type mice (C57BL/6) were infected with S. japonicum, and differences in miR-181a expression between BALB/c mice and M. fortis over different time points post-infection (0, 3, 7, 10 and 14 dpi) were compared. MiR-181a mimic, miR-181a inhibitor and irrelevant miRNA, as well as lipopolysaccharide (LPS), a TLR4 receptor ligand, were used to transfect mouse RAW264.7 macrophages. The expression levels of the TLR4 pathway-related cytokines interleukin (IL)-1β, tumor necrosis factor α (TNF-α) and IL-6 were detected by quantitative PCR analysis.
The expression of miR-181a was significantly upregulated in the serum and liver of mice infected with S. japonicum and downregulated in the serum and liver of M. fortis. T-helper cell (Th1)-type cytokines, such as TNF-α, IL-6 and IL-1β, and Th2-type cytokines, such as IL-10 and IL-4, were differentially expressed in M. fortis and BALB/c mice in the early stage of infection. The expression level of miR-181a in the serum was threefold higher in TLR4-deficient mice than in wild-type mice 10 dpi with S. japonicum. The expression of IL-1β, TNF-α and IL-6 decreased in RAW264.7 cells transfected with miR-181a mimic and increased in cells transfected with miR-181a inhibitor. miR-181a expression was downregulated and the expressions of TLR4 and three TLR4 pathway-related cytokines (IL-1β, IL-6, and TNF-α) were upregulated in RAW264.7 macrophages stimulated with the TLR4 receptor ligand LPS.
These results suggest the possibility of mutual regulation between miR-181a and the TLR4 signaling pathway during S. japonicum infection. miR-181a may regulate the expression of pro-inflammatory factors through the TLR4 receptor pathway and participate in the immunomodulatory effect of anti-S. japonicum infection.
日本血吸虫病是一种严重的人畜共患寄生虫病。初步研究表明，日本血吸虫感染易感宿主 BALB/c 小鼠和抗性宿主东方田鼠（Microtus fortis）后 10 天，肝、肺和脾组织中 microRNA-181a（miR-181a）的表达水平与感染前相比有显著差异。这种差异表明，miR-181a 的表达可能与宿主对日本血吸虫感染的早期免疫反应的调节有关，从而影响寄生虫在终末宿主中的发育和存活。
BALB/c 小鼠、东方田鼠、Toll 样受体 4（TLR4）缺陷型小鼠和野生型（C57BL/6）小鼠感染日本血吸虫，比较不同时间点（0、3、7、10 和 14 dpi）BALB/c 小鼠和东方田鼠之间 miR-181a 表达的差异。用 miR-181a 模拟物、miR-181a 抑制剂和无关 miRNA 以及 TLR4 受体配体脂多糖（LPS）转染小鼠 RAW264.7 巨噬细胞。通过定量 PCR 分析检测 TLR4 通路相关细胞因子白细胞介素（IL）-1β、肿瘤坏死因子-α（TNF-α）和 IL-6 的表达水平。
日本血吸虫感染后，小鼠血清和肝脏中 miR-181a 的表达显著上调，而东方田鼠血清和肝脏中 miR-181a 的表达下调。在感染早期，东方田鼠和 BALB/c 小鼠中 Th1 型细胞因子（如 TNF-α、IL-6 和 IL-1β）和 Th2 型细胞因子（如 IL-10 和 IL-4）表达不同。10 dpi 时，感染日本血吸虫的 TLR4 缺陷型小鼠血清中 miR-181a 的表达水平比野生型小鼠高 3 倍。miR-181a 模拟物转染的 RAW264.7 细胞中 IL-1β、TNF-α 和 IL-6 的表达降低，而 miR-181a 抑制剂转染的细胞中表达升高。LPS 刺激 RAW264.7 巨噬细胞后，miR-181a 表达下调，TLR4 及其三个 TLR4 通路相关细胞因子（IL-1β、IL-6 和 TNF-α）的表达上调。
这些结果提示 miR-181a 与日本血吸虫感染过程中的 TLR4 信号通路之间存在相互调节的可能性。miR-181a 可能通过 TLR4 受体途径调节促炎因子的表达，并参与抗日本血吸虫感染的免疫调节作用。
