| Author | Ersching, Jonatan | |
| Author | Vasconcelos, José R. | |
| Author | Ferreira, Camila P. | |
| Author | Caetano, Braulia C. | |
| Author | Machado, Alexandre de Magalhães Vieira | |
| Author | Bruna–Romero, Oscar | |
| Author | Baron, Monique A. | |
| Author | Ferreira, Ludmila R. P. | |
| Author | Cunha-Neto, Edécio | |
| Author | Rock, Kenneth L. | |
| Author | Gazzinelli, Ricardo Tostes | |
| Author | Rodrigues, Maurício M. | |
| Access date | 2022-07-05T19:11:57Z | |
| Available date | 2022-07-05T19:11:57Z | |
| Document date | 2016 | |
| Citation | ERSCHING, Jonatan et al. The Combined Deficiency of Immunoproteasome Subunits Affects Both the Magnitude and Quality of Pathogen- and Genetic Vaccination-Induced CD8(+) T Cell Responses to the Human Protozoan Parasite Trypanosoma cruzi. PLoS Pathog., v. 12, n. 4, e1005593, 2016. doi.org/10.1371/journal.ppat.1005593 | pt_BR |
| ISSN | 1553-7374 | pt_BR |
| URI | https://www.arca.fiocruz.br/handle/icict/53644 | |
| Sponsorship | FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO | pt_BR |
| Language | eng | pt_BR |
| Publisher | Public Library of Science | pt_BR |
| Rights | restricted access | pt_BR |
| Title | The Combined Deficiency of Immunoproteasome Subunits Affects Both the Magnitude and Quality of Pathogen- and Genetic Vaccination-Induced CD8(+) T Cell Responses to the Human Protozoan Parasite Trypanosoma cruzi | pt_BR |
| Type | Article | |
| DOI | 10.1371/journal.ppat.1005593 | |
| Abstract | The beta 1i, beta 2i and beta 5i immunoproteasome subunits have an important role in defining the repertoire of MHC class I-restricted epitopes. However, the impact of combined deficiency of the three immunoproteasome subunits in the development of protective immunity to intracellular pathogens has not been investigated. Here, we demonstrate that immunoproteasomes play a key role in host resistance and genetic vaccination-induced protection against the human pathogen Trypanosoma cruzi (the causative agent of Chagas disease), immunity to which is dependent on CD8(+) T cells and IFN-gamma (the classical immunoproteasome inducer). We observed that infection with T. cruzi triggers the transcription of immunoproteasome genes, both in mice and humans. Importantly, genetically vaccinated or T. cruziinfected beta 1i, beta 2i and beta 5i triple knockout (TKO) mice presented significantly lower frequencies and numbers of splenic CD8(+) effector T cells (CD8(+) CD44(high)CD62L(low)) specific for the previously characterized immunodominant (VNHRFTLV) H-2K(b)-restricted T. cruzi epitope. Not only the quantity, but also the quality of parasite-specific CD8(+) T cell responses was altered in TKO mice. Hence, the frequency of double-positive (IFN-gamma(+)/TNF+) or single-positive (IFN-gamma(+)) cells specific for the H-2K(b)-restricted immunodominant as well as subdominant T. cruzi epitopes were higher inWT mice, whereas TNF single-positive cells prevailed among CD8(+) T cells from TKO mice. Contrasting with their WT counterparts, TKO animals were also lethally susceptible to T. cruzi challenge, even after an otherwise protective vaccination with DNA and adenoviral vectors. We conclude that the immunoproteasome subunits are key determinants in host resistance to T. cruzi infection by influencing both the magnitude and quality of CD8(+) T cell responses. | pt_BR |
| Affilliation | Universidade Federal de São Paulo. Escola Paulista de Medicina. Departamento de Microbiologia, Imunologia e Parasitologia. Centro de Terapia Celular e Molecular. São Paulo, SP, Brasil | pt_BR |
| Affilliation | Universidade Federal de São Paulo. Escola Paulista de Medicina. Departamento de Microbiologia, Imunologia e Parasitologia. Centro de Terapia Celular e Molecular. São Paulo, SP, Brasil | pt_BR |
| Affilliation | Universidade Federal de São Paulo. Escola Paulista de Medicina. Departamento de Microbiologia, Imunologia e Parasitologia. Centro de Terapia Celular e Molecular. São Paulo, SP, Brasil | pt_BR |
| Affilliation | Departments of Medicine and Pathology. University of Massachusetts Medical School. Worcester. MA, United States of America | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, Brazil | pt_BR |
| Affilliation | Universidade Federal de Santa Catarina. Departamento de Microbiologia, Imunologia e Parasitologia. Florianópolis, SC, Brazil | pt_BR |
| Affilliation | Universidade de São Paulo. Faculdade de Medicina. Instituto do Coração. São Paulo, SP, Brazil | pt_BR |
| Affilliation | Universidade de São Paulo. Faculdade de Medicina. Instituto do Coração. São Paulo, SP, Brazil | pt_BR |
| Affilliation | Universidade de São Paulo. Faculdade de Medicina. Instituto do Coração. São Paulo, SP, Brazil | pt_BR |
| Affilliation | Departments of Medicine and Pathology. University of Massachusetts Medical School. Worcester. MA, United States of America | pt_BR |
| Affilliation | Departments of Medicine and Pathology. University of Massachusetts Medical School. Worcester. MA, United States of America/ Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, Brazil/Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, Brazil | pt_BR |
| Affilliation | Universidade Federal de São Paulo. Escola Paulista de Medicina. Departamento de Microbiologia, Imunologia e Parasitologia. Centro de Terapia Celular e Molecular. São Paulo, SP, Brasil | pt_BR |
