Abstract

Toxoplasma gondii is an obligate intracellular parasite capable of establishing persistent infection within the host brain and inducing severe neuropathology. Peptides are important native molecules responsible for a wide range of biological functions within the central nervous system. However, peptidome profiling in host brain during T. gondii infection has never been investigated. Using a label-free peptidomics approach (LC–MS/MS), we identified a total of 2,735 endogenous peptides from acutely infected, chronically infected and control brain samples following T. gondii infection. Quantitative analysis revealed 478 and 344 significantly differentially expressed peptides (DEPs) in the acute and chronic infection stages, respectively. Functional analysis of DEPs by Gene Ontology suggested these DEPs mainly originated from cell part and took part in cellular process. We also identified three novel neuropeptides derived from the precursor protein cholecystokinin. These results demonstrated the usefulness of quantitative peptidomics in determining bioactive peptides and elucidating their functions in the regulation of behavior modification during T. gondii infection.

Highlights

  • Human infection with the obligate intracellular parasite Toxoplasma gondii has been considered an underestimated threat [1, 2]

  • We found that remodeling of the brain peptidome by T. gondii infection was highly correlated with the severity of toxoplasmosis

  • Using H&E staining, brain samples were examined for histopathological damages caused by T. gondii infection

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Summary

Introduction

Human infection with the obligate intracellular parasite Toxoplasma gondii has been considered an underestimated threat [1, 2]. People become infected with T. gondii by eating undercooked contaminated meat or ingestion of oocysts shed by infected cats [3]. It is estimated that approximately 30% of the world’s human population carry this parasite, most people show no obvious clinical symptoms as the immune system can suppress parasite replication [4]. Toxoplasma can be reactive in immunocompromised individuals, such as AIDS patients and transplant recipients, leading to retinochoroiditis, encephalitis and even death [5]. Unborn children might undergo diseases of the nervous system and eyes if their mothers are newly infected with Toxoplasma during or just before pregnancy [6]. There are no commercial vaccines that can stop or significantly lessen the chances of Toxoplasma infection

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