Evaluation of STAT-1 and STAT-3 activation on coinfection modulation with two Trypanosoma cruzi strains in M1 and M2a polarized human macrophages

• Grant number: 19/08933-2
• Support type: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): July 01, 2019
• Status: Discontinued
• Field of knowledge: Biological Sciences - Parasitology - Protozoology of Parasites
• Principal Investigator: Renato Arruda Mortara
• Grantee: Melissa Martins de Oliveira
• Home Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated research grant: 16/15000-4 - Trypanosoma cruzi: intra and interspecific genomic variability and mechanisms of cell invasion/egress, AP.TEM

Abstract

Chagas' Disease is part of the Neglected Tropical Diseases group affecting around 8 million people worldwide and it is endemic in Latin America. The etiological agent is Trypanosoma cruzi, a digenetic parasite, that can present three illness phases in the human host: acute, indeterminate and chronic symptomatic disease. T. cruzi genetic variability, as well as its geographical distribution and host tissue tropism are determinants of the course and outcome of disease, treatment efficacy, and interaction with host's immune system. Activation or inhibition of STAT transcription factors demonstrated trypanocidal action, but the parasite can modulate this pathway in favor to its survival in intracellular environment. In addition, coinfection with more than one T. cruzi strain are relatively common both in sylvatic animals and human patients. Different strains of T. cruzi can coinfect a host cell or tissue and intermodulate each other's proliferation or quiescence, fact that leads to different parasite-host relation and disease outcome. In this context, the project aims to evaluate the coinfection with two T. cruzi strains (G and CL) compared to their monoinfection in cell-culture derived macrophages, activated by classical or alternative pathway. We intend to analyze cytokine, nitric oxide and oxidative species production from macrophages in each defined situation and correlate infection in vitro course with STAT-1 and/or STAT-3 activation.