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

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

Sahu A1, Kumar S2, Sreenivasamurthy SK3, Selvan LD4, Madugundu AK1, Yelamanchi SD5, Puttamallesh VN2, Dey G3, Anil AK6, Srinivasan A7, Mukherjee KK8, Gowda H2, Satishchandra P9, Mahadevan A10, Pandey A11, Prasad TS12, Shankar SK10.

Author information 

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

PMID:

 

25404878

 

[PubMed] 

PMCID:

 

PMC4232683