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

Sahu A, Kumar S, Sreenivasamurthy SK, Selvan LD, Madugundu AK, Yelamanchi SD, Puttamallesh VN, Dey G, Anil AK, Srinivasan A, Mukherjee KK, Gowda H, Satishchandra P, Mahadevan A, Pandey A, Prasad TS, Shankar SK - Clin Proteomics (2014)

Bottom Line: 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 pathways identified to be associated with the disease should enhance our understanding of pathogenesis in toxoplasma encephalitis.

View Article: PubMed Central - PubMed

Affiliation: Institute of Bioinformatics, International Technology Park, Bangalore, 560066 India ; Bioinformatics Centre, School of Life Sciences, Pondicherry University, Puducherry, 605014 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.

No MeSH data available.


Related in: MedlinePlus

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.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
getmorefigures.php?uid=PMC4232683&req=5

Fig1: 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.

Mentions: We carried out a quantitative proteomic analysis of the frontal lobe brain tissues from TE patients co-infected with HIV and uninfected control subjects using iTRAQ labeling followed by SCX fractionation and high resolution Fourier transform mass spectrometry. The mass spectra were searched using SEQUEST search algorithm against Human RefSeq protein database version 52, which comprised of 33,987 protein sequences. In total, we identified 3,496 proteins of which 607 proteins were differentially expressed (≥1.5-fold). Among the differentially expressed proteins, 293 and 314 proteins were found to be overexpressed and downregulated, respectively, in brain tissues of TE patients in comparison to control brain tissues (Additional file 1: Table S1). A partial list of overexpressed and downregulated proteins is provided in Tables 1 and 2, respectively. Representative MS/MS spectra of selected proteins are provided in Figure 1. We have deposited the mass spectrometry data to Human Proteinpedia and PRIDE repositories [13, 14].Table 1


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

Sahu A, Kumar S, Sreenivasamurthy SK, Selvan LD, Madugundu AK, Yelamanchi SD, Puttamallesh VN, Dey G, Anil AK, Srinivasan A, Mukherjee KK, Gowda H, Satishchandra P, Mahadevan A, Pandey A, Prasad TS, Shankar SK - Clin Proteomics (2014)

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.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4232683&req=5

Fig1: 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.
Mentions: We carried out a quantitative proteomic analysis of the frontal lobe brain tissues from TE patients co-infected with HIV and uninfected control subjects using iTRAQ labeling followed by SCX fractionation and high resolution Fourier transform mass spectrometry. The mass spectra were searched using SEQUEST search algorithm against Human RefSeq protein database version 52, which comprised of 33,987 protein sequences. In total, we identified 3,496 proteins of which 607 proteins were differentially expressed (≥1.5-fold). Among the differentially expressed proteins, 293 and 314 proteins were found to be overexpressed and downregulated, respectively, in brain tissues of TE patients in comparison to control brain tissues (Additional file 1: Table S1). A partial list of overexpressed and downregulated proteins is provided in Tables 1 and 2, respectively. Representative MS/MS spectra of selected proteins are provided in Figure 1. We have deposited the mass spectrometry data to Human Proteinpedia and PRIDE repositories [13, 14].Table 1

Bottom Line: 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 pathways identified to be associated with the disease should enhance our understanding of pathogenesis in toxoplasma encephalitis.

View Article: PubMed Central - PubMed

Affiliation: Institute of Bioinformatics, International Technology Park, Bangalore, 560066 India ; Bioinformatics Centre, School of Life Sciences, Pondicherry University, Puducherry, 605014 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.

No MeSH data available.


Related in: MedlinePlus