Susceptibility to Toxoplasma gondii proliferation in BeWo human trophoblast cells

Placenta. 2014 Jan 8. pii: S0143-4004(13)00873-4. doi: 10.1016/j.placenta.2013.12.013. [Epub ahead of print]

Susceptibility to Toxoplasma gondii proliferation in BeWo human trophoblast cells is dose-dependent of macrophage migration inhibitory factor (MIF), via ERK1/2 phosphorylation and prostaglandin E2 production

Barbosa BF¹, Paulesu L², Ietta F³, Bechi N⁴, Romagnoli R⁵, Gomes AO⁶, Favoreto-Junior S⁷, Silva DA⁸, Mineo JR⁹, Mineo TW¹⁰, Ferro EA¹¹.

INTRODUCTION:

Macrophage migration inhibitory factor (MIF) participates in the immune response to Toxoplasma gondii, triggers ERK1/2 and prostaglandin E₂ (PGE₂) activation, but there is limited information on these mechanisms in human trophoblast. The present study aimed to verify the role of MIF in the ERK1/2 phosphorylation and PGE₂ production, as well as its effect on the susceptibility to T. gondii in BeWo cells.

METHODS:

BeWo cells were treated with increasing concentrations of recombinant MIF (rMIF) and/or T. gondii-soluble tachyzoite antigen (STAg) and analyzed for ERK1/2 phosphorylation and PGE₂ production by Western blotting and ELISA, respectively. Cells were also treated with increasing concentrations of rMIF, rPGE₂, or ERK1/2 inhibitor and tested for T. gondii proliferation. The supernatants of cells treated with rPGE₂ were assayed for cytokine production by ELISA or CBA.

RESULTS:

ERK1/2 phosphorylation and PGE₂ production increased when the cells were treated with low MIF concentrations while the parasitism control occurred only at high MIF concentrations. STAg was unable to change ERK1/2 phosphorylation or PGE₂ release. BeWo cells demonstrated increased T. gondii proliferation and reduced production of pro-inflammatory cytokines when treated with PGE₂, while PD98059 diminished the parasite proliferation.

DISCUSSION:

The intracellular mechanisms triggered by MIF are dose-dependent in BeWo cells, and PGE₂ is an important factor for the persistence of T. gondii at the maternal fetal interface.

CONCLUSION:

MIF was unable to control T. gondii infection in BeWo cells at low concentrations since ERK1/2 and PGE₂ expression were activated, demonstrating a critical effect of these mediators favoring parasite proliferation.
Copyright © 2014 Elsevier Ltd. All rights reserved.

KEYWORDS:

ERK1/2, MIF, PGE(2), Toxoplasma gondii, Trophoblast cells

PMID:

24433846

[PubMed - as supplied by publisher]