Differential apoptosis in BeWo cells after infection with highly (RH) or moderately (ME49) virulent strains of Toxoplasma gondii is related to the cytokine profile secreted, the death receptor Fas expression and phosphorylated ERK1/2 expression

Placenta. 2013 Nov;34(11):973-82. doi: 10.1016/j.placenta.2013.09.005. Epub 2013 Sep 18.

Abstract

Introduction: Alterations of apoptosis are commonly associated with pregnancy complications and abortion. Modulation of apoptosis is a relevant feature of Toxoplasma gondii infection and it is related to parasite strain types. The aim of the present study was to evaluate the possible factors that are involved in the differential apoptosis of BeWo cells infected with distinct T. gondii strain types.

Methods: Human trophoblastic cells (BeWo cell line) were infected with RH or ME49 strains, the cytokine production was measured and the phosphorylation of anti-apoptotic ERK1/2 protein was analyzed. Also, cells were treated with different cytokines, infected with RH or ME49 strain, and analyzed for apoptosis index and Fas/CD95 death receptor expression.

Results: ME49-infected BeWo cells exhibited a predominantly pro-inflammatory cytokine profile, whereas cells infected with RH strain had a higher production of anti-inflammatory cytokines. Also, the incidence of apoptosis was higher in ME49-infected cells, which have been treated with pro-inflammatory cytokines compared to cells infected with RH and treated with anti-inflammatory cytokines. Moreover, Fas/CD95 expression was higher in cells infected with either ME49 or RH strain and treated with pro-inflammatory cytokines compared to anti-inflammatory cytokine treatment. The phosphorylation of ERK1/2 protein increased after 24 h of infection only with the RH strain.

Conclusion: These results suggest that opposing mechanisms of interference in apoptosis of BeWo cells after infection with RH or ME49 strains of T. gondii can be associated with the differential cytokine profile secreted, the Fas/CD95 expression and the phosphorylated ERK1/2 expression.

Keywords: Apoptosis; BeWo cells; Congenital toxoplasmosis; Toxoplasma gondii; Trophoblastic cells.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis*
  • Cell Line
  • Cytokines / genetics
  • Cytokines / metabolism*
  • Female
  • Humans
  • Mitogen-Activated Protein Kinase 1 / biosynthesis
  • Mitogen-Activated Protein Kinase 1 / metabolism*
  • Mitogen-Activated Protein Kinase 3 / biosynthesis
  • Mitogen-Activated Protein Kinase 3 / metabolism*
  • Phosphorylation
  • Placenta / immunology
  • Placenta / metabolism
  • Placenta / parasitology*
  • Placentation
  • Pregnancy
  • Pregnancy Complications, Parasitic / immunology
  • Pregnancy Complications, Parasitic / metabolism
  • Pregnancy Complications, Parasitic / parasitology
  • Pregnancy Complications, Parasitic / pathology
  • Protein Processing, Post-Translational
  • Recombinant Proteins / metabolism
  • Species Specificity
  • Toxoplasma / immunology
  • Toxoplasma / pathogenicity*
  • Toxoplasmosis / immunology
  • Toxoplasmosis / metabolism
  • Toxoplasmosis / parasitology
  • Toxoplasmosis / pathology
  • Trophoblasts / immunology
  • Trophoblasts / metabolism
  • Trophoblasts / parasitology
  • Up-Regulation
  • Virulence
  • fas Receptor / biosynthesis
  • fas Receptor / metabolism*

Substances

  • Cytokines
  • FAS protein, human
  • Recombinant Proteins
  • fas Receptor
  • MAPK1 protein, human
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3