Molecular Mechanisms of Vertical Transmission in Chagas Disease

Abstract

Chagas disease is a parasitosis caused by the protozoan parasite Trypanosoma cruzi. It is estimated that almost 7 million infected people are worldwide. In nature, there are two forms of transmission: dependent on the triatomine vector, both by depositing faeces and introduction of the parasites and by ingestion (oral route) or independent of the vector through the transplacental route (vertical transmission); in addition, human activities such as blood transfusion, organ transplantation and laboratory accidents that constitute additional sources of infection. It causes high rates of morbidity and mortality in endemic and non-endemic areas, and there is currently a global spread of the disease due to migratory flows. Chagas disease is mainly transmitted by vertical transmission (TV) in non-endemic areas and in endemic areas where vector control programs have been successful. We have isolated and characterized natural strains of Trypanosoma cruzi transmitted vertically through three generations and proceeded to study the molecular mechanisms of VT, generating a murine model of vertical transmission. We have found that these strains are specialized for vertical transmission and behave completely differently from the reference strains. In this project, we propose to dissect the molecular mechanisms of VT through the study of the maternal-fetal interface, focusing on the one hand on the genetic characteristics of the isolates and, on the other, on the modulation of the immune response that allows control of the infection but not its transplacental transmission.