Host response profile of human brain proteome in toxoplasma encephalitis co-infected with HIV

Abstract

BackgroundToxoplasma encephalitis is caused by the opportunistic protozoan parasite Toxoplasma gondii. Primary infection with T. gondii in immunocompetent individuals remains largely asymptomatic. In contrast, in immunocompromised individuals, reactivation of the parasite results in severe complications and mortality. Molecular changes at the protein level in the host central nervous system and proteins associated with pathogenesis of toxoplasma encephalitis are largely unexplored. We used a global quantitative proteomic strategy to identify differentially regulated proteins and affected molecular networks in the human host during T. gondii infection with HIV co-infection.ResultsWe identified 3,496 proteins out of which 607 proteins were differentially expressed (≥1.5-fold) when frontal lobe of the brain from patients diagnosed with toxoplasma encephalitis was compared to control brain tissues. We validated differential expression of 3 proteins through immunohistochemistry, which was confirmed to be consistent with mass spectrometry analysis. Pathway analysis of differentially expressed proteins indicated deregulation of several pathways involved in antigen processing, immune response, neuronal growth, neurotransmitter transport and energy metabolism.ConclusionsGlobal quantitative proteomic approach adopted in this study generated a comparative proteome profile of brain tissues from toxoplasma encephalitis patients co-infected with HIV. Differentially expressed proteins include previously reported and several new proteins in the context of T. gondii and HIV infection, which can be further investigated. Molecular pathways identified to be associated with the disease should enhance our understanding of pathogenesis in toxoplasma encephalitis.Electronic supplementary materialThe online version of this article (doi:10.1186/1559-0275-11-39) contains supplementary material, which is available to authorized users.

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“…In the first instance the skin preparation method comprised of powdering the frozen tissue using a pestle and mortar, further homogenisation using a glass homogeniser, sonication, filtration of interfering low molecular weight compounds. This was a method adapted from other published proteomics methods for other tissues [ 13 – 15 ]. Peptides would then be separated using reverse phase chromatography a nanoAcquity liquid chromatography system coupled to a quadrupole time-of-flight mass spectrometer (QToF Premier, Waters, Manchester) [ 12 ] (Fig.…”

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