Gut-lung axis: understanding the immune dialogue between barrier tissues in the development of disease

• Grant number: 21/06881-5
• Support type: Research Grants - Young Investigators Grants - Phase 2
• Duration: February 01, 2022 - January 31, 2027
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal researcher: Denise Morais da Fonseca
• Grantee: Denise Morais da Fonseca
• Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Assoc. researchers: Ana Marcia de Sá Guimarães ; Ana Maria Caetano de Faria ; Ana Paula Lepique ; Ana Paula Rocha Veiga ; Anderson de Sá Nunes ; Andrea Pires dos Santos ; Aristóteles Góes Neto ; Flávio Vieira Loures ; Jofer Andree Zamame Ramirez ; Maria Regina D'Império Lima ; Timothy Wesley Hand
• Associated research grant: 15/25364-0 - Impact of infection-induced immunological scarring on the long-term host metabolic homeostasis, AP.JP
• Associated scholarship(s): 22/10275-6 - Gut-lung axis: understanding the effects of immunological scar for lung tumor development, BP.DD

Abstract

Mucosal tissues are endowed with a specialized immune system with specific effector mechanisms designed to respond to the enormous range of regional challenges while maintaining tissue homeostasis. In this sense, specialized cells and immune mediators are found in each mucosal tissue. Classically, subtypes of dendritic cells, T lymphocytes, and antibody-producing B cells are differently regulated in the mucosa. Our research group has been working to identify non-classical mechanisms that act not only in maintaining tissue homeostasis but also in the communication between barrier tissues, such as the intestine and the lung. The importance of the gut-lung axis in disease control and promotion has been studied in different contexts, focusing on mechanisms involving cell trafficking, changes in the microbiota composition and microbial metabolites. In this context, at the Mucosal Immunology Laboratory, we study how episodes of infection affecting the structure of the mesentery and lymphatics impact in host immunity and metabolism, and in the integration of the immune response between the different barrier tissues. We believe that the mechanisms mediating the immunological communication between the intestinal and pulmonary mucosa have a confluence point in the mesentery. This proposal aims at understanding the mechanisms involved in the immune dialogue between mucosal tissues, particularly the gut and lung. For this, we will study the functional impact of infectious and non-infectious environmental challenges in the gut for lung immunity, focusing on the involvement of the microbiota and its metabolites, adjacent adipose tissue compartments, lymphatic vessels, and micro RNAs. This proposal will be divided into two major aims. In the first one, we will address the long-term effects of acute intestinal infection for lung immunity. In the second aim, we will study the consequences of dietary changes for lung immune homeostasis, emphasizing immunity against lung (AU)