Evaluation of the role of chemerin in activating the inflammatory response of Mycobacterium tuberculosis infected macrophages

• Grant number: 19/23446-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: June 01, 2020
• End date: February 28, 2021
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Vânia Luiza Deperon Bonato
• Grantee: Giseli Furlan Corrêa
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Tuberculosis is a chronic disease caused by the bacillus Mycobacterium tuberculosis that mainly affects the lungs. Currently, around 10 million people worldwide and 72 thousand people in Brazil, representing only 5 to 10% of infected individuals, have active or symptomatic disease. Different factors can contribute to the susceptibility to tuberculosis and among them, type 2 diabetes and obesity were associated with an increased risk of developing tuberculosis. Metainflammation triggered by both, diabetes and obesity, involves the production of inflammatory mediators such as chemerin, an adipokine capable of modulating macrophage activity. Our study hypothesis is that chemerin interferes with the innate response mediated by macrophages, making the host susceptible to the bacillus. In this context, the objective of this project is to evaluate the role of chemerin in the response of macrophages against M. tuberculosis in the context of comorbidities, diabetes associated with obesity. For this, we will evaluate the effect of chemerin on the differentiation of macrophages (M0) and in the activation of macrophages (M1) derived from bone marrow of C57BL/6 wild type mice and cultured in hyperglycemic medium. Later, we will evaluate the phagocytosis capacity and the activation of M0 macrophages, infected in vitro with M. tuberculosis, derived from bone marrow of obese mice (High Fat Diet) that present glucose intolerance, non-obese mice (Low Fat Diet) and db/db mice, established model of type 2 diabetes. Considering the contradictory role of chemerin, described in the literature as pro and also anti-inflammatory, our results aim to clarify the involvement of this adipokine in susceptibility to tuberculosis in diabetic and obese hosts. If our hypothesis is confirmed, chemerin may become a target for immunotherapy in the context of comorbidity.

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)

MARTINS, NUBIA SABRINA; DE CAMPOS FRAGA-SILVA, THAIS FERNANDA; CORREA, GISELI FURLAN; BOKO, MEDETON MAHOUSSI MICHAEL; RAMALHO, LEANDRA NAIRA ZAMBELLI; RODRIGUES, DEBORA MUNHOZ; HORI, JULIANA ISSA; COSTA, DIEGO LUIS; BASTOS, JAIRO KENUPP; BONATO, VANIA LUIZA DEPERON. Artepillin C Reduces Allergic Airway Inflammation by Induction of Monocytic Myeloid-Derived Suppressor Cells. PHARMACEUTICS, v. 13, n. 11, NOV 2021. (19/09881-6, 19/23446-0, 19/18793-3, 17/04138-8)