Journal Article

Proteomic Profiling of Mouse Liver following Acute Toxoplasma gondii Infection

Elsheikha, Hany M., Song, Hui-Qun, Ma, Jun, Zhu, Xing-Quan, He, Jun-Jun, Zhou, Dong-Hui

2016

Overview

Toxoplasma gondii remains a global public health problem. However, its pathophysiology is still not-completely understood particularly the impact of infection on host liver metabolism. We performed iTRAQ-based proteomic analysis to evaluate early liver protein responses in BALB/c mice following infection with T. gondii PYS strain (genotype ToxoDB#9) infection. Our data revealed modification of protein expression in key metabolic pathways, as indicated by the upregulation of immune response and downregulation of mitochondrial respiratory chain, and the metabolism of fatty acids, lipids and xenobiotics. T. gondii seems to hijack host PPAR signaling pathway to downregulate the metabolism of fatty acids, lipids and energy in the liver. The metabolism of over 400 substances was affected by the downregulation of genes involved in xenobiotic metabolism. The top 10 transcription factors used by upregulated genes were Stat2, Stat1, Irf2, Irf1, Sp2, Egr1, Stat3, Klf4, Elf1 and Gabpa, while the top 10 transcription factors of downregulated genes were Hnf4A, Ewsr1, Fli1, Hnf4g, Nr2f1, Pparg, Rxra, Hnf1A, Foxa1 and Foxo1. These findings indicate global reprogramming of the metabolism of the mouse liver after acute T. gondii infection. Functional characterization of the altered proteins may enhance understanding of the host responses to T. gondii infection and lead to the identification of new therapeutic targets.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Analgesics / Analysis / Animals / Biology and Life Sciences / Brain research / Cell Respiration - genetics / Down-Regulation - genetics / EGR-1 protein / Electron transport / Fatty acids / Fatty Acids - genetics / Female / Fibroblasts / FLI-1 protein / FOXO1 protein / Gene expression / Gene Expression - genetics / Gene Expression Profiling - methods / Genes / Genotype & phenotype / Genotypes / Health aspects / Hepatitis / Hepatocyte nuclear factor 4 / Immune response / Immune system / Infections / Interferon regulatory factor 1 / KLF4 protein / Laboratory animals / Lipid metabolism / Lipids / Liver / Liver - parasitology / Liver research / Medicine and Health Sciences / Metabolic Networks and Pathways - genetics / Metabolic pathways / Metabolism / Mice / Mice, Inbred BALB C / Mitochondria / Mitochondria - genetics / Mitochondria - parasitology / Parasites / Pathogenesis / Peroxisome proliferator-activated receptors / Proteins / Proteome - genetics / Proteomics / Proteomics - methods / Protozoa / Public health / Retinoid X receptor α / Rodents / Signal transduction / Signal Transduction - genetics / Signaling / Stat1 protein / Stat2 protein / Stat3 protein / Target recognition / Toxoplasma - pathogenicity / Toxoplasma gondii / Toxoplasmosis / Toxoplasmosis, Animal - genetics / Toxoplasmosis, Animal - parasitology / Transcription factors / Transcription Factors - genetics / Up-Regulation - genetics / Xenobiotics