Rat & M. fortis - lung and liver

More than 40 kinds of mammals in China are known to be naturally infected with Schistosoma japonicum (S. japonicum); Microtus fortis (M. fortis), a species of vole, is the only mammal in which the schistosomes cannot mature or cause significant pathogenic changes. In the current study, we compared the differences in pathology by Hematoxylin-eosin staining and in changes in the T cell subsets with flow cytometry as well as gene expression using genome oligonucleotide microarrays in the lung and liver, before challenge and 10 days post-infection with schistosomes in a S. japonicum-susceptible mouse model of infection, a non-susceptible rat model and the non-permissive host, M. fortis. The results demonstrated that S. japonicum promoted a more intensive immune response and more pathological lesions in M. fortis and rats than in mice. Hematoxylin-eosin staining revealed that the immune effector cells involved were mainly eosinophilic granulocytes supplemented with heterophilic granulocytes and macrophages. The analysis of splenic T cell subsets showed that CD4+ T cell subsets and the CD4+/CD8+ ratio were increased while the CD8+ T cell subsets decreased remarkably in rats; whereas the CD8+ T cell subsets were increased but the CD4+/CD8+ ratio was decreased significantly in mice. The analysis of the pattern of gene expression suggested that some immune-associated genes and apoptosis-inducing genes upregulated while some development-associated genes were downregulated in the infected M. fortis compared to the uninfected controls; the three different hosts have different response mechanisms to schistosome infection. The results of this study will be helpful for identifying the key molecules in the immune response to S. japonicum in M. fortis and for understanding more about the underlying mechanism of the response, as well as for elucidating the interaction between S. japonicum and its hosts.已知在中国境内有超过40种哺乳动物可自然感染日本血吸虫（Schistosoma japonicum，下称S. japonicum）；东方田鼠（Microtus fortis，下称M. fortis）作为一种田鼠属物种，是目前已知唯一一种体内血吸虫无法发育成熟、也不会引发显著致病性病变的哺乳动物。本研究以日本血吸虫易感的小鼠感染模型、非易感大鼠模型以及非许可宿主东方田鼠为研究对象，分别在血吸虫攻毒前与攻毒后10天，通过苏木精-伊红（Hematoxylin-eosin，HE）染色分析肺部与肝脏的病理差异，结合流式细胞术检测T细胞亚群变化，并利用基因组寡核苷酸微阵列技术分析肺、肝组织的基因表达谱差异。研究结果显示，相较于易感小鼠，日本血吸虫在东方田鼠与大鼠体内可诱发更强烈的免疫应答与更严重的病理损伤。苏木精-伊红染色结果显示，该过程中参与的免疫效应细胞以嗜酸性粒细胞为主，辅以嗜异性粒细胞与巨噬细胞。脾脏T细胞亚群分析结果表明，大鼠体内CD4+ T细胞亚群及CD4+/CD8+比值显著升高，而CD8+ T细胞亚群明显减少；小鼠体内则呈现相反变化：CD8+ T细胞亚群升高，但CD4+/CD8+比值显著降低。感染东方田鼠与未感染对照组相比，部分免疫相关基因及凋亡诱导基因表达上调，而部分发育相关基因表达下调；三种不同宿主对血吸虫感染的应答机制存在显著差异。本研究结果有助于筛选东方田鼠抗日本血吸虫免疫应答中的关键分子，深入阐明其免疫应答的潜在机制，同时也可为解析日本血吸虫与宿主之间的相互作用提供理论依据。