| Author | Fonseca, Denise Morais da | |
| Author | Silva, Célio Lopes | |
| Author | Paula, Marina Oliveira e | |
| Author | Soares, Edson Garcia | |
| Author | Marchal, Gilles | |
| Author | Horn, Cynthia | |
| Author | Bonato, Vânia Luiza Deperon | |
| Access date | 2023-03-09T02:44:00Z | |
| Available date | 2023-03-09T02:44:00Z | |
| Document date | 2007 | |
| Citation | FONSECA, Denise Morais da et al. Increased levels of interferon-c primed by culture filtrate proteins antigen and CpG-ODN immunization do not confer significant protection against Mycobacterium tuberculosis infection. Immunology, Oxford, v. 121, n. 4, p. 508-517, Aug. 2007. | en_US |
| ISSN | 1365-2567 | en_US |
| URI | https://www.arca.fiocruz.br/handle/icict/57312 | |
| Sponsorship | We would like to thank Izaı´ra Tincani Branda˜o and Ana Paula Masson for the general technical assistance provided, as well as Ana Maria da Rocha for her technical assistance in processing the histological sections. This study received financial support from the Fundac¸ão de Amparo a Pesquisa do Estado de São Paulo (FAPESP, Foundation for the Support of Research in the State of Sa˜o Paulo; grant no. 03/11303-2 and 00/09663-2), the Conselho Nacional de Desenvolvimento Cientı´fico e Tecnolo´ gico (CNPq, Council for Scientific and Technological Development), and the Rede Brasileira de Pesquisa em TB (Rede-TB, Brazilian Tuberculosis Research Network). | en_US |
| Language | eng | en_US |
| Publisher | Wiley Online Library | en_US |
| Rights | open access | en_US |
| Title | Increased levels of interferon-c primed by culture filtrate proteins antigen and CpG-ODN immunization do not confer significant protection against Mycobacterium tuberculosis infection | en_US |
| Type | Article | en_US |
| DOI | 10.1111/j.1365-2567.2007.02597.x | |
| Abstract | The results of various animal model studies of tuberculosis (TB) suggest that culture filtrate proteins (CFPs), which are antigens secreted by Mycobacterium tuberculosis, are largely responsible for improvements in TB vaccines. The great obstacle to developing protein subunit vaccines is that adjuvants are required in order to stimulate relevant protective immune responses. Acting as immune adjuvants, CpG-oligodeoxynucleotides (CpG-ODNs) promote the activation of Th1 cells and of pro-inflammatory cytokines. To evaluate the adjuvant role of CpG-ODNs in conferring enhanced immunogenic capacity and protection against M. tuberculosis, we immunized mice with CFP antigen combined with synthetic CpG-ODNs (CFP/CpG) or with incomplete Freund's adjuvant (IFA) (CFP/IFA). Immunization with CFP/CpG induced a T helper 1 (Th1)-biased response accompanied by a higher immunoglobulin G2a (IgG2a) antibody/IgG1 antibody ratio, elevated production of interferon-gamma (IFN-gamma) by spleen cells and in lungs. However, CFP/IFA-immunized mice presented higher levels of IgG1 antibodies, as well as increased production of IFN-gamma, interleukin (IL)-5, and IL-10 by spleen cells, together with lower levels of IFN-gamma in the lungs. Despite the stronger Th1 response seen in both groups, believed to be necessary for protection against TB, only mice immunized with CFP/IFA were protected after M. tuberculosis infection. Lung histology revealed that lung parenchyma were better preserved in CFP/IFA-immunized mice, which also presented intense lymphocyte recruitment to the lesion, whereas CFP/CpG-immunized mice presented severe pulmonary injury accompanied by necrosis. Based on the data presented, we discuss the widely accepted paradigm that high levels of IFN-gamma are directly correlated with protection against experimental TB. | en_US |
| Affilliation | University of São Paulo. Ribeirão Preto School of Medicine. Department of Biochemistry and Immunology. Tuberculosis Research Centre. Ribeirão Preto, SP, Brazil. | en_US |
| Affilliation | University of São Paulo. Ribeirão Preto School of Medicine. Department of Biochemistry and Immunology. Tuberculosis Research Centre. Ribeirão Preto, SP, Brazil. | en_US |
| Affilliation | University of São Paulo. Ribeirão Preto School of Medicine. Department of Biochemistry and Immunology. Tuberculosis Research Centre. Ribeirão Preto, SP, Brazil. | en_US |
| Affilliation | University of São Paulo. Ribeirão Preto School of Medicine. Department of Pathology. Ribeirão Preto, SP, Brazil. | en_US |
| Affilliation | Institute Pasteur. Laboratoire de Référence des Mycobacteries. Paris, France. | en_US |
| Affilliation | Oswaldo Cruz Foundation. Evandro Chagas Clinical Research Institute. Rio de Janeiro, RJ, Brazil. | en_US |
| Affilliation | University of São Paulo. Ribeirão Preto School of Medicine. Department of Biochemistry and Immunology. Tuberculosis Research Centre. Ribeirão Preto, SP, Brazil. | en_US |
| Subject | Tuberculosis | en_US |
| Subject | Culture filtrate proteins | en_US |
| Subject | CpG oligodeoxynucleotides | en_US |
| Subject | Vaccine | en_US |
| Subject | Adjuvant | en_US |
| e-ISSN | 1365-2567 | |
| xmlui.metadata.dc.subject.ods | 03 Saúde e Bem-Estar | |
