Parasites, Hosts and Diseases

The Korea Society for Parasitology and Tropical Medicine (대한기생충학·열대의학회)
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Adenosine A3 Receptor Mediates ERK1/2- and JNK-Dependent TNF-α Production in Toxoplasma gondii-Infected HTR8/SVneo Human Extravillous Trophoblast Cells

  • Ye, Wei (Department of Obstetrics and Gynecology, Affiliated Hospital of Guangdong Medical University) ;
  • Sun, Jinhui (Department of Gastroenterology, Affiliated Hospital of Guangdong Medical University) ;
  • Li, Chunchao (Department of Gastroenterology, Affiliated Hospital of Guangdong Medical University) ;
  • Fan, Xuanyan (Department of Gastroenterology, Affiliated Hospital of Guangdong Medical University) ;
  • Gong, Fan (Stem Cell Research and Cellular Therapy Center, Affiliated Hospital of Guangdong Medical University) ;
  • Huang, Xinqia (Stem Cell Research and Cellular Therapy Center, Affiliated Hospital of Guangdong Medical University) ;
  • Deng, Mingzhu (Stem Cell Research and Cellular Therapy Center, Affiliated Hospital of Guangdong Medical University) ;
  • Chu, Jia-Qi (Stem Cell Research and Cellular Therapy Center, Affiliated Hospital of Guangdong Medical University)
  • Received : 2020.07.13
  • Accepted : 2020.07.26
  • Published : 2020.08.31
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Abstract

Toxoplasma gondii is an intracellular parasite that causes severe disease when the infection occurs during pregnancy. Adenosine is a purine nucleoside involved in numerous physiological processes; however, the role of adenosine receptors in T. gondii-induced trophoblast cell function has not been investigated until now. The goal of the present study was to evaluate the intracellular signaling pathways regulated by adenosine receptors using a HTR-8/SVneo trophoblast cell model of T. gondii infection. HTR8/SVneo human extravillous trophoblast cells were infected with or without T. gondii and then evaluated for cell morphology, intracellular proliferation of the parasite, adenosine receptor expression, TNF-α production and mitogen-activated protein (MAP) kinase signaling pathways triggered by adenosine A3 receptor (A3AR). HTR8/SVneo cells infected with T. gondii exhibited an altered cytoskeletal changes, an increased infection rate and reduced viability in an infection time-dependent manner. T. gondii significantly promoted increased TNF-α production, A3AR protein levels and p38, ERK1/2 and JNK phosphorylation compared to those observed in uninfected control cells. Moreover, the inhibition of A3AR by A3AR siRNA transfection apparently suppressed the T. gondii infection-mediated upregulation of TNF-α, A3AR production and MAPK activation. In addition, T. gondii-promoted TNF-α secretion was dramatically attenuated by pretreatment with PD098059 or SP600125. These results indicate that A3AR-mediated activation of ERK1/2 and JNK positively regulates TNF-α secretion in T. gondii-infected HTR8/SVneo cells.

Keywords

References

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