3D cultures to understand host-parasite interactions.

• Grant number: 23/06066-5
• Support Opportunities: Research Grants - Visiting Researcher Grant - International
• Start date: February 15, 2024
• End date: March 14, 2024
• Field of knowledge: Biological Sciences - Parasitology - Protozoology of Parasites
• Principal Investigator: Ariel Mariano Silber
• Grantee: Ariel Mariano Silber
• Visiting researcher: Valeria Sonia Tekiel
• Visiting researcher institution: Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Argentina
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 21/12938-0 - Amino acid metabolism in Trypanosoma cruzi: a toolbox to survive in hostile environments, AP.TEM

Abstract

Trypanosoma cruzi, the etiological agent of Chagas' disease, produces a chronic illness whose symptoms generally appear ten or more years after the initial infection. However, the colonization of the different target tissues by the parasite is an event that takes place during the early infection, when the bloodstream circulating trypomastigotes disseminates to the different organs. Therefore, the knowledge of the process of parasite dissemination that leads to the invasion of target tissues is of paramount importance, and it could be the clue to develop alternative strategies to control the infection and/or prevent disease. How T. cruzi transmigrates and spreads within tissues has been virtually unexplored, and was the subject of research in Dr. Tekiel's laboratory in recent years. The development of cultures resembling physiological environments, like 3D spheroid cultures, represent an accurate model to reproduce in vitro the conditions encountered by the trypomastigotes in vivo, which cannot be resembled by monolayer cultures. By employing this model we demonstrated that there is a link between the depth of dissemination of parasites into spheroids (i.e. its ability to transmigrate), and the in vivo virulence of different T. cruzi strains, suggesting that the higher virulence of certain strains could be related to their better ability to efficiently transmigrate across extracellular matrix and tissues. The transmigration capacity seems to be an intrinsic characteristic of each strain that is dependent on several factors, including the differential expression of membrane proteins and on parasite motility. Being the parasite's motility closely related with energy metabolism, a current hypothesis is that different biochemical pathways could be differentially regulated in virulent and non-virulent strains. The main goal of the proposed visit of Dr Tekiel to Dr Silber's laboratory, is to transfer the 3D culture model of spheroids, which is a powerful platform to study the host - parasite interaction. (AU)