Changes in Mitochondrial Metabolism and Bioenergetics by Trypanosoma cruzi in Congenital Chagas' Infection

Congenital Chagas’ infection is a global public health problem that affects more than 5% of babies born from chronically infected mothers. Decades ago, Chagas’s disease and congenital infection was a situation exclusively of endemic areas mainly from Mexico, Central and South America. However, due to increased immigration, condition has been identified in developed countries like the USA, Canada and Europe. Despite its relative importance, the etiology and mechanism of transmission from the mother to the offspring are not well understood. However, early diagnosis of the infection and prompt treatment of newborns is key as in most cases, early treatment can prevent progression of the disease and is curative in most of cases. To understand the vertical transmission process of T. cruzi, in this study, we aimed to examine the early metabolic perturbations and changes in mitochondrial bioenergetics of T. cruzi infection in human placental cells. HTR-8/SVneo and SGHPL-5 first trimester human extra villous trophoblasts were infected with T. cruzi (Sylvio X10) and changes in mitochondrial metabolism and bioenergetics were assessed with a Seahorse XFe24 Extracellular Flux Analyzer. Also, levels of ROS were detected using Mito-SOX and fluorescence. In addition, we also examined the role of innate immunity by co-treating cells with pro-inflammatory proteins and cytokines known to have a role in the infection process like IFN-γ, TNF-α and IL-6. We found that T. cruzi infection alone, was not enough to induce significant changes in mitochondrial metabolism and bioenergetics and to increase ROS generation in placental cells. However, T. cruzi infection in combination with IFN-γ, TNF-α and IL-6 exerted a drastic effect in trophoblast mitochondrial bioenergetics and ROS production, suggesting that innate immunity is crucial in congenital transmission and progression of the disease.