Proteomic analysis of mouse liver lesions at all three stages of Echinococcus granulosus infection

细粒棘球绦虫感染小鼠三个阶段肝脏病变的蛋白质组学分析

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作者:Nan Jiang, Yang Chen, Teng Li, Yeting Sun, Yaxin Su, Ying Wang, Yujuan Shen, Jianping Cao

Abstract

Echinococcus granulosus, a zoonotic parasite, can severely damage host health or even lead to host death. In humans, early diagnosis of E. granulosus infection is difficult because the initial stages of the infection tend to be asymptomatic, this delays treatment and worsens prognosis in most patients. Herein, we present a comprehensive, temporal proteomic atlas of the liver at three stages of E. granulosus infection and analyze the changes in the proteome of host focal lesions; this atlas may provide an overview of the effects of E. granulosus in the host, as well as the interactions between them. We identified 3,197 proteins from mice model at 1, 3, and 6 months after E. granulosus infection; of these proteins, 760 were differentially expressed (520 upregulated; 240 downregulated). Moreover, 228 differentially expressed proteins were screened through cluster analysis and classified into four clusters according to their changing trends. Subsequently, candidate molecules related to cyst invasion, growth, candidate pathways and proteins related to angiogenesis were noted to demonstrate important value in mouse liver. Next, we used western blotting to verify the presence of the aforementioned proteins in mouse liver. In the later stages, E. granulosus infection was noted to result in significant enrichment of crucial proteins facilitating protoscoleces growth and development and inhibition of amino acid and lipid metabolic enzyme expression in mouse liver; it was also noted to transform host metabolism by weakening oxidative phosphorylation and enhancing glycolysis. In conclusion, we explored the molecular mechanisms underlying the parasitic processes of E. granulosus through proteomic analysis. Our results provide evidence that may enable the exploration of core regulatory targets for early and effective diagnosis and immunotherapy of E. granulosus infection, as well as parasite-host interactions involved in cystic echinococcosis development.

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