Effect of an episode of acute gastrointestinal infection on pathogenesis and progression of type 1 diabetes mellitus

• Grant number: 20/16648-3
• Support Opportunities: Scholarships in Brazil - Master
• Effective date (Start): June 01, 2021
• Effective date (End): June 30, 2023
• Field of knowledge: Biological Sciences - Immunology
• Principal Investigator: Denise Morais da Fonseca
• Grantee: Letícia Gama e Silva Calixtro
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

The gastrointestinal tract houses several commensal microorganisms that actively participate in the modulation of the host's metabolism. In addition to the microbiota, this tissue receives several daily antigens from the diet, so a highly specialized immune system is needed, which allows the host to tolerate the microbiota and diet antigens and to develop responses against potential pathogens. This balance between the immune system and microbiota is essential for maintaining homeostasis in the intestinal tissue and disturbances in this balance are commonly observed in patients with autoimmune diseases, such as type 1 diabetes mellitus (DM1). Previous work by our group showed that infection by the bacterium Yersinia pseudotuberculosis leaves an immune scar in the intestine, even after its complete elimination, which is associated with the breakdown of the intestinal mucosa barrier and the lymphatic system, leading to a deviation of the migration route of intestinal dendritic cells for draining lymph nodes and, ultimately, blocking the induction of canonical adaptive responses. In addition, unpublished results from our group indicate the presence of an inflammatory infiltrate in the pancreas of C57BL animals after infection by Y. pseudotuberculosis. However, this event per se does not lead to the development of spontaneous DM1. Thus, in this project, the impact of Y. pseudotuberculosis infection on the development of autoimmune diabetes in susceptible individuals, the mechanisms and cells involved in this process will be investigated, in addition to assessing the mechanisms that are leading to the appearance of the inflammatory infiltrate in the pancreas. For this, an animal model of autoimmune diabetes induced by multiple doses of streptozotocin and NOD mice, which develop diabetes spontaneously, will be used. (AU)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

CALIXTRO, Letícia Gama e Silva. Effect of an episode of acute gastrointestinal infection on the pathogenesis and progression of type 1 diabetes mellitus. 2023. Master's Dissertation - Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) São Paulo.