LPS-mediated activation of TLR4 controls Toxoplasma gondii growth in human trophoblast cell (BeWo) and human villous explants in a dependent-manner of TRIF, MyD88, NF-κB and cytokines

We evaluated the influence of the Toll-like receptor (TLR)-4 pathways on BeWo, JEG-3 and HTR-8/SVneo cells, as well as in human villous explants infected with Toxoplasma gondii. Cells and explants were stimulated with LPS for 24 or 48 h and processed for the MTT assay, and expression of TLR4 was evaluated by confocal microscopy. In addition, we used peptides that inhibit MyD88 or TRIF, and inhibitor to NF-κB. Finally, the parasite proliferation was verified, and ELISA was performed to verify the cytokine production. As results, LPS did not induce toxicity in cells and explants. However, LPS triggered a reduction in T. gondii proliferation only in BeWo cells and explants. Additionally, LPS downmodulated IL-10, TGF-β1 and TNF, but upregulated IFN-γ in BeWo cells. For explants, LPS induced high levels of IL-10, TGF-β1 and IFN-γ. Finally, it was observed that the inhibition of TRIF and NF-κB increased parasitism and modulated TGF-β1 in BeWo cells, while the inhibition of MyD88 and NF-κB increased T. gondii infection and modulated IFN-γ in explants. It can be concluded that the TLR4 pathway is important for the control of T. gondii replication in BeWo cells and villous explants, in a dependent-manner of TRIF, MyD88, NF-κB and cytokines. •Activation of TLR4 decreases T. gondii infection in BeWo and villous explants.•Activation of TLR4 triggers cytokine modulation in infected BeWo and explants.•T. gondii infection is modulated by TRIF or MyD88 and NF-кB in BeWo and explants.