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Clin Proteomics. 2014 Nov 1;11(1):39. doi: 10.1186/1559-0275-11-39. eCollection 2014.

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

Author information

1
Institute of Bioinformatics, International Technology Park, Bangalore, 560066 India ; Bioinformatics Centre, School of Life Sciences, Pondicherry University, Puducherry, 605014 India.
2
Institute of Bioinformatics, International Technology Park, Bangalore, 560066 India.
3
Institute of Bioinformatics, International Technology Park, Bangalore, 560066 India ; Manipal University, Madhav Nagar, Manipal, 576104 India.
4
Institute of Bioinformatics, International Technology Park, Bangalore, 560066 India ; Amrita School of Biotechnology, Amrita University, Kollam, 690525 India.
5
Institute of Bioinformatics, International Technology Park, Bangalore, 560066 India ; School of Biotechnology, KIIT University, Bhubaneswar, 751024 India.
6
Armed Forces Medical College, Pune, 411040 India.
7
Department of Pharmacology, Postgraduate Institute of Medical Education & Research, Chandigarh, 160012 India.
8
Department of Neurosurgery, Postgraduate Institute of Medical Education & Research, Chandigarh, 160012 India.
9
Department of Neurology, National Institute of Mental Health and Neurosciences, Bangalore, 560029 India.
10
Department of Neuropathology, National Institute of Mental Health and Neurosciences, Bangalore, 560029 India ; Human Brain Tissue Repository, Neurobiology Research Centre, National Institute of Mental Health and Neurosciences, Bangalore, 560029 India.
11
McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205 USA ; Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 1205 USA ; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21205 USA ; The Sol Goldman Pancreatic Cancer Research Center, Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205 USA.
12
Institute of Bioinformatics, International Technology Park, Bangalore, 560066 India ; Bioinformatics Centre, School of Life Sciences, Pondicherry University, Puducherry, 605014 India ; Manipal University, Madhav Nagar, Manipal, 576104 India ; Amrita School of Biotechnology, Amrita University, Kollam, 690525 India ; NIMHANS-IOB Proteomics and Bioinformatics Laboratory, Neurobiology Research Centre, National Institute of Mental Health and Neurosciences, Bangalore, 560029 India.

Abstract

BACKGROUND:

Toxoplasma 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.

RESULTS:

We 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.

CONCLUSIONS:

Global 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.

KEYWORDS:

Chronic meningitis; Immunosuppression; LTQ-Orbitrap Velos; Neuroinfections; Opportunistic infections; iTRAQ labeling

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