Gut-lung axis: understanding the effects of immunological scar for lung tumor development

• Grant number: 22/10275-6
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: September 01, 2022
• End date: January 31, 2027
• Field of knowledge: Biological Sciences - Immunology
• Principal Investigator: Denise Morais da Fonseca
• Grantee: Leonardo Mandu Gonçalves
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 21/06881-5 - Gut-lung axis: understanding the immune dialogue between barrier tissues in the development of disease, AP.JP2

Abstract

Colorectal Cancer (CRC) is one of the deadliest intestinal diseases, with approximately 1 million victims worldwide per year, and its incidence is high, with approximately 2 million cases per year, representing an enormous challenge to public health. Several mechanisms are studied to understand the etiology of this disease and improve patient survival, such as infectious episodes that affect intestinal homeostasis. Our group showed that after resolution of certain types of acute gastrointestinal infections, often considered harmless to the host, occurs permanent remodeling of the immune and lymphatic systems in the gastrointestinal tract and adjacent organs, such as the mesentery, resulting in chronic local inflammation that blocks specific regulators responses of the intestinal mucosa. Previous results from our group show that in this environment of chronic inflammation there is an increase in the susceptibility to development of Inflammatory Bowel Diseases (IBDs), which made us hypothesize that the same would happen with CRC. However, preliminary results showed the opposite, the previous infection protected the development of CRC, but resulted in development of lung tumors in mice. Currently, the gut-lung axis is widely studied, since it presents a traffic of immune cells, metabolites and microbiota, which make changes in either end of the axis may be related to the development of diseases. Our hypothesis is that alterations in the immunological dialogue in the gut-lung axis reflect in the establishment of CRC and Lung Cancers. To study this, we will use a CRC induction model, by azoxymethane, and several models of Lung Cancer induction, including urethane carcinogenesis, in mice previously infected with the bacteria Yersinia pseudotuberculosis. The results obtained in this project will help to understand the etiology of Intestinal and Lung Cancers in light of the immunological dialogue between the gut and lung after exposure to pathogens. (AU)