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Role of P2X7 receptor in modulation of lung immune response induced by hypervirulent mycobacteria

Grant number: 12/22587-0
Support Opportunities:Scholarships in Brazil - Master
Effective date (Start): February 01, 2013
Effective date (End): January 31, 2015
Field of knowledge:Biological Sciences - Immunology - Cellular Immunology
Principal Investigator:Maria Regina D'Império Lima
Grantee:Caio César Barbosa Bomfim
Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil


Tuberculosis is a public health problem. About one-third of the world population is infected with Mycobacteria tuberculosis and 10% of themdevelop the disease. Recent study conducted by our research group showed that mice deficient in P2X7 purinergic receptor (P2X7R) had a considerable attenuated pneumonia and pulmonary necrosis induced by hypervirulent mycobacteria (MP287/03 strains of Mycobacterium bovis and Beijing 1471 of M. tuberculosis). P2X7R is a sensor of extracellular ATP and its activation induces cell migration and activation of inflammasome, leading to production of proinflammatory cytokines (IL-1² and IL-18) and cell death by necrosis or pironecrosis. This project intends to further characterize the role of P2X7R in the development of tuberculosis through evaluating: 1) Effects of the P2X7R inhibitor Brilliant Blue G (BBG) on disease development; 2) Involvement of P2X7R on leukocyte migration to the lungs and development of pulmonary necrosis; 3) Role of P2X7R in vitroon the death of infected and non-infected macrophages. This study may contribute to understand the mechanisms involved in the P2X7R-mediated pathogenesis of the disease, opening the perspectives for the development of new therapeutic approaches aiming to attenuate the severe forms of tuberculosis.

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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)
BARBOSA BOMFIM, CAIO CESAR; AMARAL, EDUARDO PINHEIRO; CASSADO, ALEXANDRA DOS ANJOS; SALLES, ERIKA MACHADO; DO NASCIMENTO, ROGERIO SILVA; LASUNSKAIA, ELENA; HIRATA, MARIO HIROYUKI; ALVAREZ, JOSE MARIA; D'IMPERIO-LIMA, MARIA REGINA. P2X7 receptor in Bone Marrow-Derived cells aggravates Tuberculosis caused by hypervirulent Mycobacterium bovis. FRONTIERS IN IMMUNOLOGY, v. 8, . (12/22587-0, 14/22986-8, 15/20432-8, 13/07140-2)
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
BOMFIM, Caio César Barbosa. Role of P2X7 receptor in modulation of lung immune response induced by hypervirulent mycobacteria.. 2015. Master's Dissertation - Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) São Paulo.

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