title: Modulation of angiogenic factor VEGF by DNA-hsp65 vaccination in a murine CNS tuberculosis model.
abstract: Tuberculosis (TB) is a serious public health problem. Development of experimental models and vaccines are essential to elucidate physiopathological mechanisms and to control the disease. Vascular endothelial growth factor (VEGF) is a potent activator of vascular permeability and angiogenesis. VEGF seems to participate in breakdown of the blood brain-barrier (BBB) in tuberculous meningitis (TBM), contributing to worsening of disease. Therefore, the objective here was to extent the characterization of our previously described murine model of central nervous system TB (CNS-TB) by describing the VEGF participation in the CNS disease, and suggesting a vaccination plan in mice. Plasmid encoding DNA protein antigen DNA-hsp65 has been described as a protector against TB infection and was used here to test its effectiveness in the prevention of VEGF production and TB disease. Vaccinated mice and its controls were injected with Mycobacterium bovis bacillus Calmette-Guerin (BCG) in cerebellum. Four weeks after BCG injection, mice were perfused and brains were paraffin-embedded for VEGF expression analysis. We observed VEGF immunohistochemical expression in TBM and granulomas in non-vaccinated mice. The DNA-hsp65 treatment blocked the expression of VEGF in mice TBM. Therefore, our murine model indicated the VEGF participation in the physiopathology of CNS-TB and the potential prevention of the DNA-hsp65 in the disease progression.
authors.affiliation: Department of Neuroscience, University of São Paulo at Ribeirão Preto School of Medicine, Ribeirão Preto, SP, Brazil. fabiola.zucchi@gmail.com
authors.forename: Fabíola C R
authors.initials: FC
authors.lastname: Zucchi
authors.forename: Ana Maria C
authors.initials: AM
authors.lastname: Tsanaclis
authors.forename: Quintino
authors.initials: Q
authors.lastname: Moura-Dias
authors.forename: Célio L
authors.initials: CL
authors.lastname: Silva
authors.forename: Adriana
authors.initials: A
authors.lastname: Pelegrini-da-Silva
authors.forename: Luciano
authors.initials: L
authors.lastname: Neder
authors.forename: Osvaldo M
authors.initials: OM
authors.lastname: Takayanagui
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology*; D002526:Cerebellar Diseases / Q000378:metabolism / Q000517:prevention & control; D002531:Cerebellum / Q000378:metabolism; D018834:Chaperonin 60 / Q000235:genetics / Q000276:immunology*; D004195:Disease Models, Animal; D007115:Immunization Schedule; D008297:Male; D051379:Mice; D009163:Mycobacterium bovis; D016862:Tuberculoma, Intracranial / Q000378:metabolism / Q000517:prevention & control; D032581:Tuberculosis Vaccines / Q000276:immunology*; D020306:Tuberculosis, Central Nervous System / Q000378:metabolism* / Q000517:prevention & control; D014390:Tuberculosis, Meningeal / Q000378:metabolism / Q000517:prevention & control; D019444:Vaccines, DNA / Q000276:immunology*; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis*
chemical_list: D001426:Bacterial Proteins; D018834:Chaperonin 60; D032581:Tuberculosis Vaccines; D019444:Vaccines, DNA; D042461:Vascular Endothelial Growth Factor A; C074119:heat-shock protein 65, Mycobacterium; C467480:vascular endothelial growth factor A, mouse