Study of the tissue-specific response during exposure of the intestinal mucosa to bacterial toxins

• Grant number: 19/13916-0
• Support Opportunities: Scholarships in Brazil - Doctorate
• Effective date (Start): November 01, 2019
• Effective date (End): December 31, 2023
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Denise Morais da Fonseca
• Grantee: Caio Loureiro Salgado
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated scholarship(s): 21/15185-2 - Molecular and purinergic mechanisms involved in the gut-lung axis dialogue through exposure to the Escherichia coli-derived toxin - LT1, BE.EP.DR

Abstract

The mucosal tissues of the organism are composed of cellular barriers that interface the organism with the external environment, such as the intestinal mucosa, which has close contact with beneficial microbial communities that ensure efficient digestion and absorption and also ensures protection against pathogens. To establish effective anatomical and functional barriers against different microorganisms, including the commensal bacteria themselves, the intestinal mucosa and associated lymphoid tissue encompass highly complex cellular networks capable of fine regulation to avoid exacerbated immune responses, which may culminate with dysbiosis of the resident microbiota. Therefore, maintaining the integrity of the intestinal mucosa is crucial for the body's homeostasis. Similarly to the intestinal mucosa, we also have the pulmonary mucosa, which is constantly exposed to antigens and airborne pathogens. For a long time, the function of the immune system associated with the mucosal tissues was studied in a compartmentalized way, as if there was no communication between the cellular infiltrate in the different sites. With this in view, recent studies point to the hypothesis of communication between the intestinal and pulmonary mucosae. Mediators derived from the gastrointestinal tract may interfere with the homeostasis of distant tissues, including the lung. On the other hand, conditions such as malnutrition, infections or a breakdown in the integrity of the intestinal mucosa would compromise the immune response in the lung tissue. Although studies demonstrate this fact, its mechanisms of communication still remain incognito. Using the murine model of heat-Labile Toxin (LT) exposure produced by enterotoxigenic Escherichia coli, responsible for several episodes of diarrhea in children and adults, we propose in the present project to understand the immunological communication between different mucosal tissues. To do this, we will use LT together with a known antigen to evaluate the innate and antigen-specific immune responses in the intestine and their interference in the immunological homeostasis in the lung. In addition, we believe that the understanding of cellular trafficking pathways and mechanisms that mediate the immune dialogue between different mucosal tissues may contribute to understanding the regulation of the protective and pathological response during infections and inflammatory processes in barrier tissues. As a functional impact of this enteric-pulmonary dialogue, we will study its influence on the development of allergic inflammation and immunity against pulmonary pathogens. (AU)

Scientific publications

(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, 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)