Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 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

Apeksha Sahu  1 , Satwant Kumar  2 , Sreelakshmi K Sreenivasamurthy  3 , Lakshmi Dhevi N Selvan  4 , Anil K Madugundu  1 , Soujanya D Yelamanchi  5 , Vinuth N Puttamallesh  2 , Gourav Dey  3 , Abhijith K Anil  6 , Anand Srinivasan  7 , Kanchan K Mukherjee  8 , Harsha Gowda  2 , Parthasarathy Satishchandra  9 , Anita Mahadevan  10 , Akhilesh Pandey  11 , Thottethodi Subrahmanya Keshava Prasad  12 , Susarla Krishna Shankar  10
Affiliations

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

Apeksha Sahu et al. Clin Proteomics. .

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.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Representative MS/MS spectra of peptides of differentially expressed proteins: A) Major histocompatibility complex, class I, B (HLA-B) protein is upregulated 4.4-fold in toxoplasma encephalitis brain tissues when compared to controls. B) Alpha-1 antitrypsin (SERPINA1) protein is upregulated by 3.0-fold in toxoplasma encephalitis brain tissues when compared with control. C) Ras homolog family member G (RHOG) protein is downregulated by 2.5-fold in toxoplasma encephalitis brain tissues when compared with control. D) CD9 molecule (CD9) is downregulated by 2.0-fold in toxoplasma encephalitis brain tissues when compared with control.
Figure 2
Figure 2
Gene Ontology (GO) analysis of differentially regulated proteins: A) Biological processes-based analysis showed majority of the proteins involved in processes such as cell communication, growth and transport. B) Molecular function-based analysis revealed a majority of the proteins with unknown functions. However, a significant number were seen with transporter and catalytic activities among others.
Figure 3
Figure 3
Biological network analysis of differentially expressed proteins using GeneSpring identified deregulated BDNF pathway: Nineteen proteins involved in the BDNF pathway were differentially expressed including the downregulation of the BDNF receptor protein – NTRK2. Proteins involved in BDNF mediated lamellipodia formation and neurite outgrowth were downregulated whereas proteins involved in BDNF mediated synaptic plasticity were overexpressed.
Figure 4
Figure 4
Immunohistochemistry-based validation of differentially expressed proteins in toxoplasma encephalitis co-infected with HIV: A) Histiocytic elements in the toxoplasma lesion strongly expressed HLA-B, while the pale zones represent the necrotic acellular zones, B) Higher magnification highlights strong expression of HLA-B in the perivascular histiocytes, C) The expression of RHOG is marginally downregulated in the histiocytes and newly formed capillary endothelia, D) Control brain has low expression of alpha-1 antitrypsin (SERPINA1) in glial cells and a necrotic vessel wall, E) In the case of toxoplasma encephalitis the glial cells, the micro vessels and histiocytes expressed alpha-1 antitrypsin strongly unlike the control.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Tan IL, Smith BR, von Geldern G, Mateen FJ, McArthur JC. HIV-associated opportunistic infections of the CNS. Lancet Neurol. 2012;11:605–617. doi: 10.1016/S1474-4422(12)70098-4. - DOI - PubMed
    1. Hakko E, Ozkan HA, Karaman K, Gulbas Z. Analysis of cerebral toxoplasmosis in a series of 170 allogeneic hematopoietic stem cell transplant patients. Transpl Infect Dis. 2013;15:575–580. doi: 10.1111/tid.12138. - DOI - PubMed
    1. Mittal V, Ichhpujani RL. Toxoplasmosis - an update. Trop Parasitol. 2011;1:9–14. doi: 10.4103/2229-5070.72109. - DOI - PMC - PubMed
    1. Kumar GG, Mahadevan A, Guruprasad AS, Kovoor JM, Satishchandra P, Nath A, Ranga U, Shankar SK. Eccentric target sign in cerebral toxoplasmosis: neuropathological correlate to the imaging feature. J Magn Reson Imaging. 2010;31:1469–1472. doi: 10.1002/jmri.22192. - DOI - PMC - PubMed
    1. Bhattacharyya S, Khurana S, Dubey ML. Anti-Toxoplasma gondii antibody detection in serum and urine samples by enzyme-linked immunosorbent assay in HIV-infected patients. Indian J Pathol Microbiol. 2013;56:20–23. doi: 10.4103/0377-4929.116143. - DOI - PubMed