Analysis of the development of glucose intolerance and insulin resistance post-immunological scar induced by acute intestinal infection

• Grant number: 19/07771-9
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): May 01, 2019
• Effective date (End): April 30, 2021
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Denise Morais da Fonseca
• Grantee: Bernardo de Castro Oliveira
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 15/25364-0 - Impact of infection-induced immunological scarring on the long-term host metabolic homeostasis, AP.JP

Abstract

Acute infections represent frequent and intense tissue disorders from which organs have to recover quickly so that there is no loss of function. Sites of high antigenic exposure, such as the intestinal mucosa, are particularly exposed to acute infections where pathogens, commensal microorganisms, and environmental antigens share transiently the same inflammatory microenvironment. Whereas in order to eliminate the pathogen, regulatory responses are generally inhibited during these infections, such encounters may interfere with the ability of the immune system to distinguish between benign versus pathogenic and self elements versus non-self elements which can lead to the induction and maintenance of chronic tissue inflammation in the absence of the pathogen. We have recently shown that a single episode of acute infection by Yersinia pseudotuberculosis can irreversibly affect homeostasis and immunity in the intestinal mucosa through a phenomenon that we call "immunological scar" which includes remodeling of the mesentery, interruption of the dialogue intestinal mucosa-host and loss of compartmentalization of the microbiota. However, it is not known what impact these events have on organs/tissues distant from the infectious site. This issue becomes even more important in the current increase in the incidence of systemic inflammatory diseases and metabolic diseases, such as diabetes. Thus, this project hypothesis is that acute infections can lead to loss of the intestinal microbiota compartmentalization, promoting chronic inflammation in distant sites to the initial infection, such as adipose tissue, and this fact may interfere with the pancreatic function leading to the development of sugar metabolism defects, such as intolerance to glucose and insulin resistance. Thus, in this project, we will use the "immunological scar" experimental model induced by Y. pseudotuberculosis to study the acute gastrointestinal infections effect on the sugar metabolism.

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)

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)