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

Apeksha Sahu, Satwant Kumar, Sreelakshmi K. Sreenivasamurthy, Lakshmi Dhevi N. Selvan, Anil K. Madugundu, Soujanya D. Yelamanchi, Vinuth N. Puttamallesh, Gourav Dey, Abhijith K. Anil, Anand Srinivasan, Kanchan K. Mukherjee, Harsha Gowda, Parthasarathy Satishchandra, Anita Mahadevan, Akhilesh Pandey, Thottethodi Subrahmanya Keshava Prasad, Susarla Krishna Shankar

Research output: Contribution to journalArticle

11 Scopus citations

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.

Original languageEnglish (US)
JournalClinical Proteomics
Volume11
Issue number1
DOIs
StatePublished - 2014

Keywords

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

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry

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    Sahu, A., Kumar, S., Sreenivasamurthy, S. K., Selvan, L. D. N., Madugundu, A. K., Yelamanchi, S. D., Puttamallesh, V. N., Dey, G., Anil, A. K., Srinivasan, A., Mukherjee, K. K., Gowda, H., Satishchandra, P., Mahadevan, A., Pandey, A., Prasad, T. S. K., & Shankar, S. K. (2014). Host response profile of human brain proteome in toxoplasma encephalitis co-infected with HIV. Clinical Proteomics, 11(1). https://doi.org/10.1186/1559-0275-11-39