Toll-like receptor-2 mediates local innate immune response against Trypanosoma cruzi in ex vivo infected human placental chorionic villi explants. (December 2017) - Castillo, Christian
Abstract: Background: Congenital Chagas disease is caused by the protozoan parasite Trypanosoma cruzi that must cross the placental barrier during transmission. The trophoblast constitutes the first tissue in contact with the maternal-blood circulating parasite. Importantly, the congenital transmission rates are low, suggesting the presence of local placental defense mechanisms. On the other hand, the placenta is considered an immune regulatory organ since it acts as a modulator of fetal and maternal immune responses. We have previously proposed that local placental factors, such as the epithelial turnover of the trophoblast and the innate immune response initiated by Toll -like receptors (TLRs), might prevent parasite infection and congenital transmission. Here, we studied in an ex vivo infected human placental chorionic villi explant HPCVE model, the relationship between TLR-2 activation in response to T. cruzi trypomastigotes, the secreted profile of cytokines, the integrity of the placental barrier and the expression of trophoblast turnover markers. Results: TLR-2 inhibition increases the parasite induced histopathological damage, prevents secretion of IL-6 and IL-10, decreases expression of PCNA (proliferation marker) and of β-hCG (differentiation marker) while increasing caspase 3 activity (cell death marker). Conclusion: Our results suggest that TLR-2 is not only involved in the local secretion of cytokines but also regulates, at least partially, the trophoblast turnover. Graphical abstract: Highlights: T. cruzi infection induces TLR-2 expression in human placenta explants. T. cruzi induces cytokine secretion in human placenta explants. TLR-2 inhibition increases tissue damage and modifies IL-6/10 secretion. TLR-2 inhibition decreases T. cruzi -induced proliferation and differentiation. TLR-2 inhibition increases T. cruzi -induced cell death.