iTRAQ-based Quantitative Proteomics Analysis Identifies Host Pathways Modulated during Toxoplasma gondii Infection in...

Area of Science:

• Proteomics
• Infectious Disease Research
• Animal Health

Background:

• Toxoplasma gondii is a major cause of foodborne illness, with undercooked pork being a significant risk factor.
• Toxoplasmosis in pigs leads to substantial societal and economic burdens.
• Understanding host-pathogen interactions is crucial for developing effective control strategies.

Purpose of the Study:

• To identify cellular proteins and pathways affected by T. gondii infection in pigs using advanced proteomics.
• To analyze differential protein expression in various pig tissues at different infection stages.
• To discover potential therapeutic targets for combating T. gondii in swine.

Main Methods:

• Isobaric tags for relative and absolute quantification (iTRAQ) labeling coupled with LC-MS/MS for proteomic profiling.
• Parallel reaction monitoring (PRM)-based LC-MS/MS for validating protein expression levels.
• Weighted gene co-expression network analysis (WGCNA) to identify protein interaction modules.

Main Results:

• Significant numbers of differentially expressed proteins (DEPs) were identified in brain, liver, lung, mesenteric lymph nodes (MLNs), and spleen at 6 and 18 days post-infection.
• Immune response proteins were generally upregulated, while metabolic processes were downregulated in infected livers.
• A specific protein co-expression module (pink) strongly correlated with infection status.
• 163 potential anti-T. gondii proteins (PATPs) were identified, with HSP70.2 and PDIA3 showing in vitro efficacy in reducing parasite burden.

Conclusions:

• This study provides a comprehensive proteomic landscape of T. gondii infection in pigs.
• Key proteins involved in host defense mechanisms against T. gondii were identified.
• HSP70.2 and PDIA3 represent promising candidates for further investigation as therapeutic agents against porcine toxoplasmosis.