Transcriptomic analysis of mouse liver reveals a potential hepato-enteric pathogenic mechanism in acute Toxoplasma gondii infection

Abstract

BackgroundToxoplasma gondii is a worldwide spread pathogen which can infect all tissues of its host. The transcriptomic responses of infected brain and spleen have been reported. However, our knowledge of the global transcriptomic change in infected liver is limited. Additionally, T. gondii infection represents a highly dynamic process involving complex biological responses of the host at many levels. Herein, we describe such processes at a global level by discovering gene expression changes in mouse livers after acute infection with T. gondii ToxoDB#9 strain.ResultsGlobal transcriptomic analysis identified 2,758 differentially expressed transcripts in infected liver, of which 1,356 were significantly downregulated and 1,402 upregulated. GO and KEGG database analyses showed that host immune responses were upregulated, while the metabolic-related processes/pathways were downregulated, especially xenobiotic metabolism, fatty acid metabolism, energy metabolism, and bile biosynthesis and secretion. The metabolism of more than 800 chemical compounds including anti-Toxoplasma prescribed medicines were predicted to be modulated during acute T. gondii infection due to the downregulation of enzymes involved in xenobiotic metabolism.ConclusionsTo the best of our knowledge, this is the first global transcriptomic analysis of mouse liver infected by T. gondii. The present data indicate that during the early stage of liver infection, T. gondii can induce changes in liver xenobiotic metabolism, upregulating inflammatory response and downregulating hepatocellular PPAR signaling pathway, altering host bile biosynthesis and secretion pathway; these changes could enhance host intestinal dysbacteriosis and thus contribute to the pathological changes of both liver and intestine of infected mice. These findings describe the biological changes in infected liver, providing a potential mechanistic pathway that links hepatic and intestinal pathologies to T. gondii infection.Electronic supplementary materialThe online version of this article (doi:10.1186/s13071-016-1716-x) contains supplementary material, which is available to authorized users.

iTRAQ-based Quantitative Proteomics Analysis Identifies Host Pathways Modulated during Toxoplasma gondii Infection in Swine

“…GO and KEGG pathway analyses have shown that vesicle related processes were upregulated in most infected tissues, including brain, spleen, lung and MLNs (Supplementary Files S2-S6). However, vesicle-related processes were downregulated in infected liver at 6 dpi (Supplementary File S3), which disagrees with upregulation of the vesicle-related processes detected previously in the liver of infected mice [17,44]. However, downregulation of the metabolic process of infected pig liver in the present study was also observed in the mouse model [17,44].…”

“…However, vesicle-related processes were downregulated in infected liver at 6 dpi (Supplementary File S3), which disagrees with upregulation of the vesicle-related processes detected previously in the liver of infected mice [17,44]. However, downregulation of the metabolic process of infected pig liver in the present study was also observed in the mouse model [17,44]. About 190 proteins, involved in metabolic processes, were differentially expressed in the infected livers, most of them downregulated (Supplementary File S3).…”

A Transcriptome Analysis: Various Reasons of Adverse Pregnancy Outcomes Caused by Acute Toxoplasma gondii Infection

“…More recently, He et al (2016b) analyzed the transcriptomic changes in the spleen of infected mice to elucidate the immune responses against T. gondii infection. Later, they evaluated the transcriptomic gene expressions in the liver of infected mice during the early stages of T. gondii infection (He et al, 2016a). However, data on the global transcriptomic changes in uterine tissues of mouse with acute T. gondii infection are highly deficient, despite of its crucial importance.…”

Evidence for host genetic regulation of altered lipid metabolism in experimental toxoplasmosis supported with gene data mining results

“…RNa-seq data in liver in infection with PYS (type I/III) parasites (data from He et al [14]). Panel A–extract from cholesterol biosynthetic pathway and export (adapted from KEGG pathways).…”