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Antigen-presenting cells transfected with Hsp65 messenger RNA fail to treat experimental tuberculosis
Rocha, C.D.; Trombone, A.P.F.; Lorenzi, J.C.C.; Almeida, L.P.; Gembre, A.F.; Padilha, E.; Ramos, S.G.; Silva, C.L.; Coelho-Castelo, A.A.M..
  • Rocha, C.D.; Universidade de São Paulo. Faculdade de Medicina de Ribeirão Preto. Departamento de Bioquímica e Imunologia. Ribeirão Preto. BR
  • Trombone, A.P.F.; Universidade de São Paulo. Faculdade de Medicina de Ribeirão Preto. Departamento de Bioquímica e Imunologia. Ribeirão Preto. BR
  • Lorenzi, J.C.C.; Universidade de São Paulo. Faculdade de Medicina de Ribeirão Preto. Departamento de Bioquímica e Imunologia. Ribeirão Preto. BR
  • Almeida, L.P.; Universidade de São Paulo. Faculdade de Medicina de Ribeirão Preto. Departamento de Bioquímica e Imunologia. Ribeirão Preto. BR
  • Gembre, A.F.; Universidade de São Paulo. Faculdade de Medicina de Ribeirão Preto. Departamento de Bioquímica e Imunologia. Ribeirão Preto. BR
  • Padilha, E.; Universidade de São Paulo. Faculdade de Medicina de Ribeirão Preto. Departamento de Bioquímica e Imunologia. Ribeirão Preto. BR
  • Ramos, S.G.; Universidade de São Paulo. Faculdade de Medicina de Ribeirão Preto. Departamento de Bioquímica e Imunologia. Ribeirão Preto. BR
  • Silva, C.L.; Universidade de São Paulo. Faculdade de Medicina de Ribeirão Preto. Departamento de Bioquímica e Imunologia. Ribeirão Preto. BR
  • Coelho-Castelo, A.A.M.; Universidade de São Paulo. Faculdade de Medicina de Ribeirão Preto. Departamento de Bioquímica e Imunologia. Ribeirão Preto. BR
Braz. j. med. biol. res ; 45(12): 1183-1194, Dec. 2012. ilus, mapas, tab
Article in English | LILACS | ID: lil-659642
Responsible library: BR1.1
ABSTRACT
In the last several years, the use of dendritic cells has been studied as a therapeutic strategy against tumors. Dendritic cells can be pulsed with peptides or full-length protein, or they can be transfected with DNA or RNA. However, comparative studies suggest that transfecting dendritic cells with messenger RNA (mRNA) is superior to other antigen-loading techniques in generating immunocompetent dendritic cells. In the present study, we evaluated a new therapeutic strategy to fight tuberculosis using dendritic cells and macrophages transfected with Hsp65 mRNA. First, we demonstrated that antigen-presenting cells transfected with Hsp65 mRNA exhibit a higher level of expression of co-stimulatory molecules, suggesting that Hsp65 mRNA has immunostimulatory properties. We also demonstrated that spleen cells obtained from animals immunized with mock and Hsp65 mRNA-transfected dendritic cells were able to generate a mixed Th1/Th2 response with production not only of IFN-γ but also of IL-5 and IL-10. In contrast, cells recovered from mice immunized with Hsp65 mRNA-transfected macrophages were able to produce only IL-5. When mice were infected with Mycobacterium tuberculosis and treated with antigen-presenting cells transfected with Hsp65 mRNA (therapeutic immunization), we did not detect any decrease in the lung bacterial load or any preservation of the lung parenchyma, indicating the inability of transfected cells to confer curative effects against tuberculosis. In spite of the lack of therapeutic efficacy, this study reports for the first time the use of antigen-presenting cells transfected with mRNA in experimental tuberculosis.
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Full text: Available Index: LILACS (Americas) Main subject: Bacterial Proteins / Tuberculosis / RNA, Messenger / Tuberculosis Vaccines / Mycobacterium tuberculosis / Antigen-Presenting Cells Limits: Animals Language: English Journal: Braz. j. med. biol. res Journal subject: Biology / Medicine Year: 2012 Type: Article Affiliation country: Brazil Institution/Affiliation country: Universidade de São Paulo/BR

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Full text: Available Index: LILACS (Americas) Main subject: Bacterial Proteins / Tuberculosis / RNA, Messenger / Tuberculosis Vaccines / Mycobacterium tuberculosis / Antigen-Presenting Cells Limits: Animals Language: English Journal: Braz. j. med. biol. res Journal subject: Biology / Medicine Year: 2012 Type: Article Affiliation country: Brazil Institution/Affiliation country: Universidade de São Paulo/BR