MicroRNA expression profiles associated with anti-schistosome features in Microtus fortis

Microtus fortis (M. fortis) is the only mammal in which the growth, development and maturation of schistosomes (Schistosoma japonicum) is prevented, resulting in the failure of the parasite to mature and complete its life cycle. MicroRNAs (miRNAs) are a class of endogenous, non-coding small RNAs, has been found to introduce a whole new layer of gene regulation in eukaryotes. The anti-schistosomiasis mechanosm of M. fortis may require the participation of miRNA-mediated gene expression. In the present study, the difference pathological change of different tissue such as liver, spleen and lung of M. fortis were observed by using haematoxylin-eosin staining. Also, the miRNA expression in different tissue of M. fortis and mice before challenge and 10 days post-infection with schistosomes were first compared using microRNA microarray analysis. Histological analyses showed that S. japonicum infection in M. fortis resulted in more intensive inflammatory response and pathologic change than mice. The microarray investigations showed that 388 miRNAs detected common expressed in the two species, and 11 miRNAs in liver, 25 miRNAs in spleen and 28 miRNAs in lung differentially expressed in non-permissive M. fortis while increased, decreased or nearly fixed in mice. Further studies of the differentially expressed miRNAs demonstrated that many important signal pathway were triggered after the S. japonicum infection in M. fortis rather than the mouse, such as the metabolism of some nutrient material such as fatty-acid, cholesterol, lipid, insulin, and carbohydrate; immune response such as B and T cell differentiation, monocyte differentiation, the inflammation, NF-kappaB binding, even the in innate immune system; Cell differentiation and apoptosis such as erythrocytic differentiation and targeting proapoptotic and antiapoptotic proteins. These results may provide new insights into general mechanisms of regulation in non-permissive M. fortis, exploit the potential miRNA regulatory networks and the interaction between parasites and different hosts, which provide valuable new information on schistosome biology and valuable information for the better understanding of schistosome development and host-parasite interactions. We collected liver, spleen and lung from control and 10 days post-infection with schistosomes of M. fortis, mice and rat, respectively.东方田鼠（Microtus fortis, M. fortis）是目前已知唯一可阻断日本血吸虫（Schistosoma japonicum）生长、发育及成熟过程的哺乳动物，能够使该寄生虫无法完成成熟阶段并终结其生活史。微小RNA（MicroRNAs, miRNAs）是一类内源性非编码小RNA，已被证实为真核生物的基因调控提供了全新的层级。东方田鼠的抗血吸虫感染机制可能依赖于miRNA介导的基因表达调控。 本研究首先通过苏木精-伊红染色，观察了东方田鼠肝、脾、肺等不同组织的病理性变化差异；同时采用微小RNA芯片分析，首次对比了感染血吸虫前以及感染后10天时，东方田鼠与小鼠不同组织中的miRNA表达谱差异。 组织学分析结果显示，相较于小鼠，日本血吸虫感染东方田鼠后引发的炎症反应与病理性变化更为剧烈。芯片检测结果表明，两个物种间共检测到388个共同表达的miRNA；在非易感宿主东方田鼠体内，肝脏中有11个、脾脏中有25个、肺脏中有28个miRNA呈现差异表达，而在小鼠体内这些miRNA则表现为上调、下调或表达水平基本恒定。 对差异表达miRNA的进一步研究显示，相较于小鼠，日本血吸虫感染东方田鼠后触发了诸多重要信号通路：包括脂肪酸、胆固醇、脂质、胰岛素及碳水化合物等营养物质代谢通路；B细胞与T细胞分化、单核细胞分化、炎症反应、核因子κB（NF-kappaB）结合乃至先天免疫系统相关的免疫应答通路；以及红细胞分化、靶向促凋亡与抗凋亡蛋白相关的细胞分化与凋亡通路。 本研究结果可为解析非易感宿主东方田鼠的调控通用机制提供新视角，有助于挖掘潜在的miRNA调控网络以及寄生虫与不同宿主间的互作机制，为阐明血吸虫生物学特性、深入理解血吸虫发育过程及宿主-寄生虫互作关系提供宝贵的新信息。本研究分别采集了东方田鼠、小鼠和大鼠的对照组及血吸虫感染后10天的肝、脾、肺组织。