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

Clinical Proteomics

Susarla Krishna Shankar⁹  Thottethodi Subrahmanya Keshava Prasad⁴  Akhilesh Pandey³  Anita Mahadevan⁹  Parthasarathy Satishchandra²  Harsha Gowda^1,10  Kanchan K Mukherjee^1,11  Anand Srinivasan⁵  Abhijith K Anil⁷  Gourav Dey⁸  Vinuth N Puttamallesh^1,10  Soujanya D Yelamanchi⁶  Anil K Madugundu¹  Lakshmi Dhevi N Selvan⁴  Sreelakshmi K Sreenivasamurthy⁸  Satwant Kumar^1,10  Apeksha Sahu¹ 

[1] Bioinformatics Centre, School of Life Sciences, Pondicherry University, Puducherry 605014, India;Department of Neurology, National Institute of Mental Health and Neurosciences, Bangalore 560029, India;The Sol Goldman Pancreatic Cancer Research Center, Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA;Amrita School of Biotechnology, Amrita University, Kollam 690525, India;Department of Pharmacology, Postgraduate Institute of Medical Education & Research, Chandigarh 160012, India;School of Biotechnology, KIIT University, Bhubaneswar 751024, India;Armed Forces Medical College, Pune 411040, India;Manipal University, Madhav Nagar, Manipal 576104, India;Human Brain Tissue Repository, Neurobiology Research Centre, National Institute of Mental Health and Neurosciences, Bangalore 560029, India;Institute of Bioinformatics, International Technology Park, Bangalore 560066, India;Department of Neurosurgery, Postgraduate Institute of Medical Education & Research, Chandigarh 160012, India

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

Others  :  1092813
DOI  :  10.1186/1559-0275-11-39

 received in 2014-02-05, accepted in 2014-09-02,  发布年份 2014

【 摘 要 】

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.

【 授权许可】

   
2014 Sahu et al.; licensee BioMed Central Ltd.

【 图 表 】

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