Immunological scar development and impairment of the tissue-specific immune response after COVID-19

• Grant number: 23/00532-4
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Effective date (Start): March 01, 2023
• Effective date (End): February 28, 2025
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Denise Morais da Fonseca
• Grantee: Marcelo Valdemir de Araujo
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 21/06881-5 - Gut-lung axis: understanding the immune dialogue between barrier tissues in the development of disease, AP.JP2

Abstract

Infectious episodes can definitively compromise tissue-specific immune responses, particularly in the mucosa. At the Laboratory of Mucosal Immunology (ICB/USP), we studied the long-term effects of acute episodes of infection in the gut and lung mucosa. After certain models of acute gastrointestinal infection (Y. pseudotuberculosis, T. gondii and Citrobacter rodentium) there may be an increase in permeability and leakage of the contents of the lymphatic vessels that drain the gut (FONSECA et al., 2015). In fact, defined intestinal pathogens are capable to promote local lymphatic system remodeling, disrupting therefore, the immune communication in the gut. This immunological scar can compromise tissue immunity in the long term and can be found in the form of impaired oral tolerance induction after bacterial infection (for example, by Yersina pseudotuberculosis), impaired both thymic stroma function and naïve lymphocyte generation (for example, by Toxoplasma gondii) or even impairment of the lymphocyte repertoire (for example, by the measles or influenza virus). Considering the SARS-Cov-2, the virus responsible for the current COVID-19 pandemic, causes an intense inflammation not only in the lung, but also in the gut mucosa, we hypothesized that acute pulmonary inflammation by coronaviruses may induce changes in the mesentery and vice versa, leading to chronic remodeling and generating an immunological scar.This work plan includes the subproject described in the AIM III of the JP-2 proposal and aims at characterizing the function of gut-associated immune system following COVID-19 in order to study the development of immunological scarring and impairment of tissue-specific immune response after coronavirus infection.