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

• Grant number: 21/06881-5
• Support Opportunities: Research Grants - Young Investigators Grants - Phase 2
• Start date: February 01, 2022
• End date: January 31, 2027
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Denise Morais da Fonseca
• Grantee: Denise Morais da Fonseca
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated 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): 25/01138-3 - Contextual effect and safety of probiotic consumption in intestinal inflammatory processes, BP.DD; 24/23654-0 - Contribution of different visceral adipose compartments to oral mucosal vaccine response, BP.DD; 24/14290-5 - Mechanisms involved in protection against Metabolic Syndrome after infection with Yersinia pseudotuberculosis, BP.MS; + associated scholarships 24/10030-9 - Contribution of gamma delta T lymphocytes involved in pulmonary neutrophilia induced by ketogenic diet., BP.MS; 24/17283-0 - Low protein diet effect over allergic asthma development, BP.IC; 24/15712-0 - Gut-lung Axis: understanding the effects of immunological scar for lung tumor development, BP.PD; 24/09982-5 - Effect of ketogenic diet on the development of experimental asthma, BP.IC; 23/15980-2 - Impact of infection-induced immunological scar for the development of colon-rectal cancer, BP.IC; 23/04035-5 - Contribution of adipose tissue compartments to oral vaccine response, BP.MS; 23/00189-8 - Effect of selenium-enriched probiotic on mucosal tissues, BP.MS; 23/00532-4 - Immunological scar development and impairment of the tissue-specific immune response after COVID-19, BP.PD; 23/00534-7 - Gut-lung Axis: understanding the effects of immunological scar for lung tumor development, BP.PD; 22/10275-6 - Gut-lung axis: understanding the effects of immunological scar for lung tumor development, BP.DD - associated scholarships

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)

Scientific publications

(5)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

SAYEDAHMED, EKRAMY E.; ARAUJO, MARCELO VALDEMIR; SILVA-PEREIRA, TAIANA TAINA; CHOTHE, SHUBHADA K.; ELKASHIF, AHMED; ALHASHIMI, MARWA; WANG, WEN-CHIEN; SANTOS, ANDREA P.; NAIR, MEERA SURENDRAN; GONTU, ABHINAY; et al. Impact of an autophagy-inducing peptide on immunogenicity and protection efficacy of an adenovirus-vectored SARS-CoV-2 vaccine. MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT, v. 30, p. 14-pg., 2023-09-14. (19/13916-0, 19/12691-4, 20/09149-0, 20/07251-2, 21/06881-5, 21/02736-0)

DE SOUZA, ALEX JUNIOR SOUZA; DE SOUZA, ANTONIO FRANCISCO; ZIMPEL, CRISTINA KRAEMER; AYUPE, MARINA CACADOR; DE ARAUJO, MARCELO VALDEMIR; MACHADO, RAFAEL RAHAL GUARAGNA; SALLES, ERIKA; SALGADO, CAIO LOUREIRO; TAVARES, MARIANA SILVA; SILVA-PEREIRA, TAIANA TAINA; et al. Hepatic endotheliitis in Golden Syrian hamsters (Mesocricetus auratus) experimentally infected with SARS-CoV-2. Revista do Instituto de Medicina Tropical de São Paulo, v. 66, p. 6-pg., 2024-01-01. (21/02736-0, 21/06881-5, 20/06409-1, 23/00532-4, 17/24769-2, 20/07251-2, 19/10896-8, 20/09149-0, 16/20045-7)

DE SOUZA, WILLIAM DANILO FERNANDES; DA FONSECA, DENISE MORAIS; SARTORI, ALEXANDRINA. COVID-19 and Multiple Sclerosis: A Complex Relationship Possibly Aggravated by Low Vitamin D Levels. CELLS, v. 12, n. 5, p. 28-pg., 2023-03-01. (21/06881-5)

DE SOUZA, WILLIAM DANILO FERNANDES; ZORZELLA-PEZAVENTO, SOFIA FERNANDA GONCALVES; AYUPE, MARINA CACADOR; SALGADO, CAIO LOUREIRO; OLIVEIRA, BERNARDO DE CASTRO; MOREIRA, FRANCIELLY; DA SILVA, GUILHERME WILLIAM; MURARO, STEFANIE PRIMON; DE SOUZA, GABRIELA FABIANO; PROENCA-MODENA, JOSE LUIZ; et al. Lung Inflammation Induced by Inactivated SARS-CoV-2 in C57BL/6 Female Mice Is Controlled by Intranasal Instillation of Vitamin D. CELLS, v. 12, n. 7, p. 24-pg., 2023-04-01. (19/13916-0, 20/04558-0, 19/07771-9, 21/12768-7, 19/12691-4, 21/06881-5)

SIQUEIRA, MIRIAN KRYSTEL DE; ANDRADE-OLIVEIRA, VINICIUS; STACY, APOLLO; GUIMARAES, JOAO PEDRO TORRES; ALBERCA-CUSTODIO, RICARDO WESLEY; CASTOLDI, ANGELA; SANTOS, JAQUELINE MARQUES; DAVOLI-FERREIRA, MARCELA; MENEZES-SILVA, LUISA; TURATO, WALTER MIGUEL; et al. Infection-elicited microbiota promotes host adaptation to nutrient restriction. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, v. 120, n. 4, p. 8-pg., 2023-01-24. (21/06881-5, 17/02298-8, 18/15981-0, 15/25364-0, 18/00458-0, 16/08385-7, 18/14562-4, 17/14209-0)