Impact of previous acute gastrointestinal infections on the progression of experimental colitis

• Grant number: 21/01984-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): May 01, 2021
• Effective date (End): June 30, 2022
• Field of knowledge: Biological Sciences - Immunology
• Principal Investigator: Denise Morais da Fonseca
• Grantee: Leonardo Mandu Gonçalves
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Inflammatory bowel diseases (IBD) affect millions of people worldwide, representing a substantial public health challenge. Several mechanisms have been studied to explain the etiology of such diseases and help in their management, including infectious diseases that affect gut homeostasis. Our group have shown that, after the resolution of defined types of acute intestinal infection, there is permanent remodeling of the immune and lymphatic systems in the gastrointestinal tract, which leads to microbiota translocation to the mesentery, resulting in a chronic local inflammation that blocks the specific regulatory responses of the intestinal mucosa. We hypothesized that this process, which we call 'immunological scar', may be involved in the etiology of IBD, particularly colitis. Therefore, we will study in this project whether previous acute gastrointestinal infections interfere within the course of experimental colitis. For this, we will use two models previously described in the literature for inducing experimental colitis by dextran sulfate sodium (DSS): an acute and a chronic model in animals previously submitted to oral infection by the bacterium Yersinia pseudotuberculosis. The results obtained in this project will help to understand the etiology of IBDs in the light of environmental factors, particularly, exposure to pathogens.