Influência da infecção por Toxoplasma gondii na interação entre vilos placentários humanos e astrócitos (U-373 MG)

Abstract

Congenital toxoplasmosis, caused by the protozoan Toxoplasma gondii, can result in significant alterations in the fetal central nervous system. Although the placenta constitutes an essential barrier against vertical transmission, it also acts as an immunologically active organ capable of releasing mediators that may influence fetal tissues. This study investigated the role of soluble factors produced by first- and third-trimester human placental villi, infected or not with T. gondii, in modulating the response of U-373 MG cells, used as an astrocyte-like cell model. Conditioned media obtained from placental explants were used to evaluate cell viability, production of reactive oxygen species (ROS) and cytokines, ICAM-1 expression, and cell susceptibility to parasite adhesion, invasion, and proliferation. Third-trimester placental villi showed greater susceptibility to T. gondii infection than first-trimester villi. Placental infection also altered the profile of soluble mediators, promoting changes in the production of pro- and anti-inflammatory cytokines. Conditioned media from infected villi reduced U-373 MG cell viability and increased ROS production, indicating that factors released by the infected placenta can alter the cellular state even in the absence of direct contact with the parasite. In addition, gestational age-dependent effects on susceptibility to infection were observed. Conditioned medium from first-trimester villi restricted T. gondii proliferation, whereas conditioned medium from infected third-trimester villi favored parasite invasion and intracellular proliferation. ICAM-1 expression and parasite adhesion were also differentially modulated between gestational periods, with increased ICAM-1 expression associated with conditioned medium from infected third-trimester villi. Collectively, these findings demonstrate that the infected placenta actively influences astrocyte-like cells and that this communication is dependent on gestational stage. These results suggest that the pathogenesis of congenital toxoplasmosis may involve not only the direct effects of parasite presence in the central nervous system, but also the action of soluble mediators originating at the maternal-fetal interface, highlighting a potential functional placenta–brain communication during T. gondii infection.