Abstract
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.
Highlights
Over one-third of human population worldwide are chronically infected with the apicomplexan protozoan parasite Toxoplasma gondii [1], and are at high risk of developing serious diseases if they became immune-compromised or when women get pregnant
Our results demonstrate that host protein involved in cellular immune defense, lipid metabolism, and intracellular transport are regulated during the early stage of T. gondii infection
Potential roles of the altered proteins in response to acute T. gondii infection in the present study corroborated the current knowledge of T. gondii infection
Summary
Over one-third of human population worldwide are chronically infected with the apicomplexan protozoan parasite Toxoplasma gondii [1], and are at high risk of developing serious diseases if they became immune-compromised or when women get pregnant. Despite great effort and much progress, toxoplasmosis remains a major threat to global health. No vaccine is available to date; anti-toxoplasma drugs are not highly effective and are associated with significant side effects [2]. The parasite is capable of developing resistance to these drugs. Novel approaches and new PLOS ONE | DOI:10.1371/journal.pone.0152022. Novel approaches and new PLOS ONE | DOI:10.1371/journal.pone.0152022 March 22, 2016
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