Resveratrol-mediated reversal of changes in purinergic signaling and immune response induced by Toxoplasma gondii infection of neural progenitor cells

  • Nathieli B. BottariEmail author
  • Micheli M. PillatEmail author
  • Maria R.C. Schetinger
  • Karine P. Reichert
  • Vanessa Machado
  • Charles E. Assmann
  • Henning Ulrich
  • Anielen Dutra
  • Vera M. Morsch
  • Taís Vidal
  • Ivana B. M. Da Cruz
  • Cinthia Melazzo
  • Aleksandro Schafer Da SilvaEmail author
Original Article


The effects of Toxoplasma gondii during embryonic development have not been explored despite the predilection of this parasite for neurons and glial cells. Here, we investigated the activation of the purinergic system and proinflammatory responses during congenital infection by T. gondii. Moreover, neuroprotective and neuromodulatory properties of resveratrol (RSV), a polyphenolic natural compound, were studied in infected neuronal progenitor cells (NPCs). For this study, NPCs were isolated from the telencephalon of infected mouse embryos and subjected to neurosphere culture in the presence of EGF and FGF2. ATP hydrolysis and adenosine deamination by adenosine deaminase activity were altered in conditions of T. gondii infection. P2X7 and adenosine A2A receptor expression rates were augmented in infected NPCs together with an increase of proinflammatory (INF-γ and TNF-α) and anti-inflammatory (IL-10) cytokine gene expression. Our results confirm that RSV counteracted T. gondii-promoted effects on enzymes hydrolyzing extracellular nucleotides and nucleosides and also upregulated P2X7 and A2A receptor expression and activity, modulating INF-γ, TNF-α, and IL-10 cytokine production, which plays an integral role in the immune response against T. gondii.


NPCs P2X7 receptor A2A receptor Cytokines Toxoplasmosis 


Financial support

This work was supported by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES/PROEX, process number 88887.186030/2018-00). HU is grateful for grant support by the São Paulo State Foundation FAPESP (Project No. 2012/50880-4) and the National Research Council CNPq. MMP is grateful for a post-doctorate fellowship granted by FAPESP (Project No. 2015/19478-3).

Compliance with ethical standards

Ethics’ committee approval

This experiment was approved by the Ethics’ Committee for Animal Experimentation of the Universidade Federal de Santa Maria (UFSM), under protocol number 9509010915.

Conflict of interest

The authors declare that they have no conflicts of interest.

Supplementary material

11302_2018_9634_MOESM1_ESM.docx (940 kb)
Fig. S1 (DOCX 940 kb)


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Copyright information

© Springer Nature B.V. 2018

Authors and Affiliations

  • Nathieli B. Bottari
    • 1
    • 2
    Email author
  • Micheli M. Pillat
    • 3
    Email author
  • Maria R.C. Schetinger
    • 1
  • Karine P. Reichert
    • 1
  • Vanessa Machado
    • 1
  • Charles E. Assmann
    • 1
  • Henning Ulrich
    • 3
  • Anielen Dutra
    • 1
  • Vera M. Morsch
    • 1
  • Taís Vidal
    • 1
  • Ivana B. M. Da Cruz
    • 4
  • Cinthia Melazzo
    • 1
  • Aleksandro Schafer Da Silva
    • 1
    • 2
    • 5
    Email author
  1. 1.Graduate Program in Toxicological Biochemical and Department of Biochemistry and Molecular BiologyUniversidade Federal de Santa Maria (UFSM)Santa MariaBrazil
  2. 2.Department of Animal ScienceUniversity of Santa Catarina StateChapecóBrazil
  3. 3.Department of Biochemistry, Institute of ChemistryUniversidade de São Paulo (USP)São PauloBrazil
  4. 4.Graduate Program in PharmacologyUniversidade Federal de Santa Maria (UFSM)Santa MariaBrazil
  5. 5.Graduate Program in Animal ScienceUniversidade do Estado de Santa Catarina (UDESC)ChapecóBrazil

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