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Animal model for analysis of the pathogenicity of Mycobacterium bovis strains and evaluation of cellular and humoral immune responses against pathogenic isolates

Grant number: 10/51150-4
Support type:Regular Research Grants
Duration: September 01, 2010 - August 31, 2012
Field of knowledge:Biological Sciences - Immunology
Principal Investigator:Maria Regina D'Império Lima
Grantee:Maria Regina D'Império Lima
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Tuberculosis remains an emergent problem of public health. One-third of the world's population is infected by Mycobacterium tuberculosis (Mtb) and 10% of them develop the disease. Brazil is the 14th country in terms of tuberculosis notifications with prevalence of 60 cases per 100.000 habitants in 2007. Bovine tuberculosis is an infectious and contagious zoonosis caused by Mycobacterium bovis (Mbv). The incidence of Mbv infection and the pathogenicity of isolates from Brazilian cattle are still poorly investigated. The fact that human beings are also susceptible to Mbv increases the interest for this disease, where infection occurs through consumption of contaminated products of animal origin. The transmission of Mbv bacillus among humans is also observed in cases of disseminated infection and results in pulmonary pathology. Thus, analyzing the virulence of Mbv isolates in Brazil is of great importance. Taking into account these considerations, we sought to establish a satisfactory animal model for screening the virulence and the immunomodulatory capacity of pathogenic Mbv strains in immunocompetent and immunodeficient hosts. The present project pretends: 1) to evaluate the degree of virulence of clinical isolates of Mbv (B2 e MP287/03), according to the in vivo and in vitro replicating capacity and the disease severity in infected mice, through the analysis of histological slides from lung, spleen and liver and survival rate; 2) to verify the immune response against these pathogenic Mbv isolates by quantifying pro- and anti-inflammatory molecules by real time RT PCR; and 3) to analyze the escape mechanisms of these pathogenic isolates in infected macrophages. (AU)

Scientific publications (6)
(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)
DA SILVA, HENRIQUE BORGES; DE SALLES, ERIKA MACHADO; LIMA-MAURO, ELIANA FAQUIM; SARDINHA, LUIZ ROBERTO; ALVAREZ, JOSE MARIA; D'IMPERIO LIMA, MARIA REGINA. CD28 deficiency leads to accumulation of germinal-center independent IgM(+) experienced B cells and to production of protective IgM during experimental malaria. PLoS One, v. 13, n. 8 AUG 27 2018. Web of Science Citations: 2.
DE SALLES, ERIKA MACHADO; DE MENEZES, MARIA NOGUEIRA; SIQUEIRA, RENAN; DA SILVA, HENRIQUE BORGES; AMARAL, EDUARDO PINHEIRO; CASTILLO-MENDEZ, SHEYLA INES; CUNHA, ISABELA; CASSADO, ALEXANDRA DOS ANJOS; VIEIRA, FLAVIA SARMENTO; NICHOLAS OLIVIERI, DAVID; TADOKORO, CARLOS EDUARDO; ALVAREZ, JOSE MARIA; COUTINHO-SILVA, ROBSON; D'IMPERIO-LIMA, MARIA REGINA. P2X7 receptor drives Th1 cell differentiation and controls the follicular helper T cell population to protect against Plasmodium chabaudi malaria. PLOS PATHOGENS, v. 13, n. 8 AUG 2017. Web of Science Citations: 15.
AMARAL, EDUARDO P.; CONCEICAO, ELISABETE L.; COSTA, DIEGO L.; ROCHA, MICHAEL S.; MARINHO, JAMOCYR M.; CORDEIRO-SANTOS, MARCELO; D'IMPERIO-LIMA, MARIA REGINA; BARBOSA, THEOLIS; SHER, ALAN; ANDRADE, BRUNO B. N-acetyl-cysteine exhibits potent anti-mycobacterial activity in addition to its known anti-oxidative functions. BMC Microbiology, v. 16, OCT 28 2016. Web of Science Citations: 14.
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.; ALVAREZ, JOSE M.; LASUNSKAIA, ELENA B.; D'IMPERIO-LIMA, MARIA REGINA. Pulmonary Infection with Hypervirulent Mycobacteria Reveals a Crucial Role for the P2X7 Receptor in Aggressive Forms of Tuberculosis. PLOS PATHOGENS, v. 10, n. 7 JUL 2014. Web of Science Citations: 39.
MOREIRA, VANESSA; TEIXEIRA, CATARINA; DA SILVA, HENRIQUE BORGES; D'IMPERIO LIMA, MARIA REGINA; DOS-SANTOS, MARIA CRISTINA. The crucial role of the MyD88 adaptor protein in the inflammatory response induced by Bothrops atrox venom. Toxicon, v. 67, p. 37-46, JUN 1 2013. Web of Science Citations: 10.
MOREIRA, VANESSA; DOS-SANTOS, MARIA CRISTINA; NASCIMENTO, NEIDE GALVAO; DA SILVA, HENRIQUE BORGES; FERNANDES, CRISTINA MARIA; D'IMPERIO LIMA, MARIA REGINA; TEIXEIRA, CATARINA. Local inflammatory events induced by Bothrops atrox snake venom and the release of distinct classes of inflammatory mediators. Toxicon, v. 60, n. 1, p. 12-20, JUL 2012. Web of Science Citations: 29.

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