Evaluation of Th9/IL-9 profile participation in Trypanosoma cruzi in vitro and in vivo infection

• Grant number: 17/17103-8
• Support Opportunities: Scholarships in Brazil - Doctorate
• Effective date (Start): June 01, 2018
• Effective date (End): April 30, 2021
• Field of knowledge: Biological Sciences - Parasitology - Protozoology of Parasites
• Principal Investigator: Renato Arruda Mortara
• Grantee: Nadjania Saraiva de Lira Silva
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Chagas disease is caused by T. cruzi parasite and affects around 8 million people in the world. Individuals infected with T. cruzi may exhibit various symptoms and in different organs, depending on parasite strain and host immune response, in which the balance of pro and anti-inflammatory cytokines contributes to the definition of the disease course. Inflammation and ROS generation are important microbicidal mechanisms in the T. cruzi containment in its initial phase, however the persistence of the parasite in certain tissues causes chronic inflammatory stimulus, stress imbalance and consequent tissue damage and fibrosis. Patients with chronic Chagas' heart disease, the main complication of T. cruzi infection, present high levels of IL-9, an important cytokine that regulates the activation of mast cells and fibrogenic inflammatory processes. Despite the scarce and controversial data on the role of IL-9 and Th9 cells, little is known about this cytokine in Chagas disease. The aim of this study is to analyze the influence of the IL-9 cytokine on macrophages and its activation in T. cruzi infection, and to evaluate whether the Th9 cell population in spleen and peritoneum is associated with murine experimental infection, tissue injury and cardiac parsite load, as well as an imbalance in oxidative stress and in the balance of pro and anti-inflammatory cytokines during the acute and chronic phases of infection. Thus, we intend to clarify if there is participation of the Th9/IL-9 profile in the immunopathology of T. cruzi infection. These data will contribute to a better understanding of the parasite-host relationship, in an attempt to elucidate part of the mechanisms involved in the different courses and symptoms of the disease.