Scholarship 10/19246-1 - Tuberculose, Virulência - BV FAPESP
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Role of inflammasome activation in development of the tuberculosis pathogeny induced by hypervirulent clinical isolates

Grant number: 10/19246-1
Support Opportunities:Scholarships in Brazil - Doctorate
Start date until: June 01, 2011
End date until: December 31, 2015
Field of knowledge:Biological Sciences - Immunology - Cellular Immunology
Principal Investigator:Maria Regina D'Império Lima
Grantee:Eduardo Pinheiro Amaral
Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated scholarship(s):13/07298-5 - Evaluation of the involvement of lysosomal cathepsins in the NLRP3-inflammasome activation induced by recombinant ESAT-6 from Mycobacterium tuberculosis, BE.EP.DR

Abstract

Tuberculosis remains an emergent problem of public health. One-third of the world's population is infected by Mycobacterium tuberculosis (Mtb). Over the years, the mycobacteria have acquired genetic mutations, which is responsible for virulence increase virulence and/or resistance to chemotherapy. Previously, we observed that hypervirulent isolates from Mtb complex have different ability to modulate the immune response in murine experimental model. We also observed that the immune response activation, characterized by a very low production of inflammatory mediators and an increase of IL-10 production, or, on the other hand, characterized by increase production of IL-1b, NO and IFN-g, may reduce mice survival. Recently, has been reported that mycobacteria are capable of inducing inflammatory response through inflammasomes activation, which resulted in IL-1b production. It also was demonstrated that IL-1b b, IL-1b /R and caspase-1 deficient mice infected with Mtb (H37Rv) had low survival, suggesting that IL-1b production is crucial for control of the infection. Therefore, we intend to investigate the role of inflammasomes activation during tuberculosis pathogenesis induced by hypervirulent clinical isolates. The present project intends: to evaluate the involvement of inflammasomes in the activation of macrophages infected by mycobacteria from Mtb complex (M. bovis MP287/03 and Mtb H37Rv and Beijing 1471), as well as, in the induction of adaptive immune response; also, to evaluate the importance of the mechanism involved in the host protection or development of severe immunopathology and the effects of dangers signals (ATP), as activators of inflammasomes in the pathogeny generated by hypervirulent clinical isolates (MP287/03 and Beijing 1471). (AU)

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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)
AMARAL, EDUARDO P.; LASUNSKAIA, ELENA B.; D'IMPERIO-LIMA, MARIA REGINA. Innate immunity in tuberculosis: how the sensing of mycobacteria and tissue damage modulates macrophage death. Microbes and Infection, v. 18, n. 1, p. 11-20, . (10/19246-1, 13/07140-2)
AMARAL, EDUARDO P.; RIBEIRO, SIMONE C. M.; LANES, VERONICA R.; ALMEIDA, FABRICIO M.; DE ANDRADE, MARCELLE R. M.; BARBOSA BOMFIM, CAIO CESAR; SALLES, ERIKA M.; BORTOLUCI, KARINA R.; COUTINHO-SILVA, ROBSON; HIRATA, MARIO H.; et al. Pulmonary Infection with Hypervirulent Mycobacteria Reveals a Crucial Role for the P2X7 Receptor in Aggressive Forms of Tuberculosis. PLOS PATHOGENS, v. 10, n. 7, . (10/51150-4, 10/19246-1)
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
AMARAL, Eduardo Pinheiro. Intervention in signaling pathways associated with cellular damage recognition to reduce the immunopathology of severe forms of tuberculosis.. 2015. Doctoral Thesis - Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) São Paulo.

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