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通过微阵列分析研究日本血吸虫感染不同阶段巨噬细胞的免疫调节基因反应。

A study of immunomodulatory genes responses to macrophages of Schistosoma japonicum infection during different stages by microarray analysis.

机构信息

Department of Parasitology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.

出版信息

Acta Trop. 2013 Sep;127(3):251-60. doi: 10.1016/j.actatropica.2013.05.012. Epub 2013 May 31.

DOI:10.1016/j.actatropica.2013.05.012
PMID:23732117
Abstract

Macrophages initiate, modulate, and also serve as final effector cells in immune responses during the course of schistosomal infections. In this study, we investigated the gene expression profile and functional changes of macrophages in immune responses against the Schistosoma japonicum by microarray analysis. Hierarchical clustering analysis demonstrated that a significant switch in gene transformation associated with a type-1 response and linked with a type-2 cytokine phenotype occurs between 4.5 and 8 weeks post-infection. Moreover, the gene profiles at 3 later time-points following egg challenge were similar in complexity and magnitude. The data also showed that there were mostly inhibition of gene expression related TLR, IFN, MHC and TNFrsf at the switch between 4.5 and 8 weeks post-infection, It is suggested that these immunomodulatory genes may be down-regulated in defense against S. japonicum eggs and granuloma pathology. The induction of alternatively activated macrophage (AAMϕ) was important for dampening the inflammation in hepatic granulomas and contributing to a decrease in cytotoxicity. The gene expressions involved in repair/remodeling during liver fibrosis were also observed after egg production. Understanding the immune mechanisms associated with parasitic resistance, pathology of parasite infection, and parasite growth will provide useful insight on host-schistosome interactions and for the control of schistosomiasis.

摘要

巨噬细胞在血吸虫感染过程中的免疫反应中启动、调节和充当最终效应细胞。在这项研究中,我们通过微阵列分析研究了针对日本血吸虫免疫反应中巨噬细胞的基因表达谱和功能变化。层次聚类分析表明,与 1 型细胞因子表型相关的基因转化在感染后 4.5 至 8 周之间发生显著转变。此外,在卵攻击后 3 个较晚的时间点,基因谱在复杂性和幅度上相似。数据还表明,在感染后 4.5 至 8 周之间的转变过程中,与 TLR、IFN、MHC 和 TNFrsf 相关的基因表达主要受到抑制,表明这些免疫调节基因可能在抵抗日本血吸虫卵和肉芽肿病理方面下调。诱导替代激活的巨噬细胞(AAMϕ)对于抑制肝肉芽肿中的炎症和降低细胞毒性很重要。在产卵后也观察到与肝纤维化过程中的修复/重塑相关的基因表达。了解与寄生虫抗性、寄生虫感染病理和寄生虫生长相关的免疫机制将为宿主-血吸虫相互作用和控制血吸虫病提供有用的见解。

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