Brain proteomic differences between wild-type and CD44- mice induced by chronic Toxoplasma gondii infection

Parasitol Res. 2018 Aug;117(8):2623-2633. doi: 10.1007/s00436-018-5954-z. Epub 2018 Jun 12.

Abstract

Chronic clinical Toxoplasma gondii (T. gondii) infection is the primary disease state that causes severe encephalitis. CD44 is a member of the cell adhesion molecule family and plays an important role in T. gondii infection. However, proteomic changes in CD44 during chronic T. gondii infection have rarely been reported. Thus, an iTRAQ-based proteomic study coupled with 2D-LC-MS/MS analysis was performed to screen CD44-related proteins during chronic T. gondii infection. As a result, a total of 2612 proteins were reliably identified and quantified. Subsequently, 259, 106, and 249 differentially expressed proteins (DEPs) were compared between CD44- mice (A) vs wild-type mice (B), B vs wild-type mice infected with T. gondii (C), and C vs CD44- mice infected with T. gondii (D). Gene ontology, KEGG pathway, and protein-protein interaction analyses were performed on the DEPs. According to the results, immune-related proteins were altered significantly among the A vs B, B vs C, and C vs D comparisons, which might indicate that chronic T. gondii infection caused changes in the host immune response. Additionally, Ca2+- and metabolism-related proteins were upregulated in C vs D, which supported the hypothesis that CD44 mediated the production of host Ca2+ and IFN-γ and that the parasite preferentially invaded cells expressing high levels of CD44. The present findings validate and enable a more comprehensive knowledge of the role of CD44 in hosts chronically infected with T. gondii, thus providing new ideas for future studies on the specific functions of CD44 in latent toxoplasmosis.

Keywords: CD44-; Differentially expressed protein (DEP); Proteomic; Toxoplasma gondii; iTRAQ.

MeSH terms

  • Animals
  • Brain / metabolism
  • Brain / parasitology
  • Chromatography, Liquid
  • Down-Regulation
  • Encephalitis / etiology*
  • Encephalitis / parasitology
  • Gene Ontology
  • Humans
  • Hyaluronan Receptors / genetics
  • Hyaluronan Receptors / metabolism*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Protein Interaction Maps
  • Proteomics*
  • Tandem Mass Spectrometry
  • Toxoplasma / physiology*
  • Toxoplasmosis / complications
  • Toxoplasmosis / metabolism*
  • Toxoplasmosis / parasitology
  • Up-Regulation
  • Zoonoses

Substances

  • Cd44 protein, mouse
  • Hyaluronan Receptors