Differential Host Gene Expression During The Infection With Three Alveolar Echinococcus From Northeast Inner Mongolia, China

At the end of last centry, Tang Chongti et al found there were three types of alveolar echinococcus in the Northeast Inner Mongolia, China. Subsequent studies indicated that they should be regarded as independent species: Echinococcus multilocularis, Echinococcus sibiricensis and Echinococcus russicensis.In this dissertation, the differential host gene expression during the infection with three alveolar echinococcus was explored.There are three parts in the paper.1. The comparative analysis of ITS sequences from three alveolar echinococcus:By using PCR technology, we amplified ITS sequences from three alveolar echinococcus. The results showed that there were at least 2 different kinds of sequences from the same type of alveolar echinococcus, especially in the ITS2 part. However, the ITSl sequences of Echinococcus sibiricensis were quite different from those of Echinococcus russicensis and Echinococcus multilocularis. As such, the clustering result showed that most of the clone sequences from the same type of alveolar echinococcus can be distinguished from another one, implying the genomic differences in these types of alveolar echinococcus.2. The study on the differential host gene expression during the infection with three alveolar echinococcus:In this part, microarray, proteomic and bioinformatic technology were used to explore the differential gene (protein) expression induced by three alveolar echinococcus. The results and discussion part are shown as in two chapters:Chapter 1: A total of 64 genes were common to infection in the liver of all three alveolar echinococcus with 73 common proteins found. GO analysis of the microarray data showed that up-regulated genes included those involved in immune response and the depressed genes were related to oxidoreductase activity and energy metabolism, which was strongly supported by the proteomic data.Chapter 2: Furthermore, analysis of the gene expression data indicated 278 genes were significantly changed in the mice infected with Echinococcus sibiricensis and Echinococcus russicensis, but not in those infected with Echinococcus multilocularis. In the 278 genes, 205 were induced including those related to immune response, apoptosis, cell differentiation, cell cycle, cell division and DNA amplification, etc. Moreover, a number of genes were only significantly up-regulated in the mice infected with Echinococcus russicensis, including those related to cell division, cytoskeleton organization and biogenesis, and DNA damage response. These genes in this infected group have a much higer expression ratio than those in the other two groups as well as the GO functional categories "cytoskeleton organization and biogenesis" and "DNA damage response" were only enriched in Echinococcus russicensis infected group.3. Developmental changes in the serum Th1/2 cytokine expression of mice infected with three alveolar echinococcus:Th1/2 cytokine expressions were examined in the serum of mice infected with three alveolar echinococcus. The results showed that TNF-αand IFN-γwere slightly induced at early stage of the infection and then remarkably up-regulated at later stage (80-100 day post infection) in all of the infected groups. Contrarily, IL-4 and IL-10 were induced only at the later stage (100 days post infecion).The expression of TNF-αand IFN-γin the mice infected with Echinococcus sibiricensis reached at the maximum at 80-100 days post infection and then remained at a relatively high level, however, it signicantly reduced in the other two groups. It implied that the Th1 type cytokines TNF-αand IFN-γfunctioned in the Echinococcus sibiricensis-induced infection with a stronger activity. As such, the expression levels of TNF-αand IFN-γwere lower in the mice infected with Echinococcus multilocularis.