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

Jun-Jun He,Xing-Quan Zhu,Hui-Qun Song,Hany M Elsheikha,Jun Ma,Si-Yang Huang

doi:10.1186/s13071-016-1716-x

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.

Highlights

Toxoplasma gondii is a worldwide spread pathogen which can infect all tissues of its host
To 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 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

Summary

Introduction

Toxoplasma gondii is a worldwide spread pathogen which can infect all tissues of its host. T. gondii infection represents a highly dynamic process involving complex biological responses of the host at many levels. 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. But probably because T. gondii spreads to the liver during the acute phase of infection, this may go unnoticed. He et al Parasites & Vectors (2016) 9:427 several hepatic pathologies, such as hepatomegaly, hepatitis, granuloma, necrosis, cholestatic jaundice and cirrhosis have been linked to T. gondii infection [5,6,7,8]. Acute T. gondii infection with RH strain in mice revealed an association between the increased number of hepatic stellate cells (HSCs) and the amount of T. gondii antigens, suggesting a regulatory role for HSCs in the pathogenesis of T. gondii-induced hepatitis [11]

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