Role of probiotic Bifidobacterium longum and alarmin IL-33 in restricting lung inflammation in obesity and tuberculosis comorbidity

• Grant number: 24/05569-6
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: June 01, 2024
• End date: March 31, 2025
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Vânia Luiza Deperon Bonato
• Grantee: Paulo Lucas Cerqueira Coelho
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 17/21629-5 - Strategies to study pulmonary inflammation during comorbidities, AP.TEM

Abstract

Tuberculosis is a heterogeneous disease that is influenced by genetic factors of the infected host, the strain of mycobacteria, social and economic factors, and comorbidities. Among the comorbidities, obesity and diabetes increase the susceptibility to developing the disease.Initially and based on the literature, I started from the hypothesis that the inflammatory response resulting from obesity and diabetes is directly linked to the increase in the magnitude of lung inflammation during infection with M. tuberculosis, and consequently, to the susceptibility to infection. Our group published two articles (Albornoz, S et al. - Journal of Pathology, 2023, and Albornoz, S et al. - Cells, 2021), resulting from the development of the subproject Subproject 3 of the Thematic: Role of the IL-1/IL axis -1R, of NLRP3, of the effect of the microbiota and the efficacy of IL-33 on lung inflammation and susceptibility to tuberculosis during metabolic dysfunctions. The focus of our study for this postdoctoral fellowship was foreseen in our Thematic schedule and is a continuation of the results published by our group (Albornoz, S et al. - Cells, 2021). In this context, we will continue with the continuity and development of the results obtained in subproject 3 (Role of the IL-1/IL-1R axis, NLRP3, the effect of the microbiota and the efficacy of IL-33 in lung inflammation and susceptibility to tuberculosis during metabolic dysfunctions.), investigating the role of the probiotic Bifidovacterium longum and the effect of IL-33 on tolerance to the pathogen and tissue damage in the obesity and tuberculosis comorbidity model.Main goalTo evaluate the role of the probiotic B. longum or recombinant IL-33 (rIL-33) in the comorbidity of obesity and tuberculosis.Specific objectives1. Evaluate lung inflammation through histological sections (H&E staining) and quantification of the inflammatory infiltrate in the lungs of lean or obese groups treated or not with probiotics, and obese groups treated or not with rIL-33;2. Evaluate the production of cytokines and the ability to control the infection of M1 or M2 macrophages infected with M. tuberculosis in the presence or absence of rIL-33,3. Quantification of Foxp3 regulatory T cells, lung inflammation and the number of bacilli in the lungs in the following experimental groups of Foxp3 GFP animals: 1- LFD (Low Fat Diet + infection with Mtb; 2- HFD (High Fat Diet - with obesity - + Mtb infection; 3- LFD (Low Fat Diet + Mtb infection + probiotic treatment; 4- HFD (High Fat Diet - with obesity - + Mtb infection + probiotic treatment;4. Evaluation of the function of regulatory T cells that will be collected from the spleen of obese and infected animals or lean and infected animals that have or have not been treated with probiotics.