Rapamycin Improves the Response of Effector and Memory CD8 + T Cells Induced by Immunization With ASP2 of Trypanosoma cruzi
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2021 |
| Outros Autores: | , , , , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Institucional da FIOCRUZ (ARCA) |
| Texto Completo: | https://www.arca.fiocruz.br/handle/icict/51822 |
Resumo: | Federal University of São Paulo. Molecular Immunology Laboratory. Center of Molecular and Cellular Therapy. São Paulo, SP, Brazil / Federal University of São Paulo. Department of Microbiology, Immunology and Parasitology. São Paulo, SP, Brazil. |
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Moraschi, Barbara FerriNoronha, Isaú HenriqueFerreira, Camila PontesCariste, Leonardo MoroMonteiro, Caroline BrandãoDenapoli, PriscilaVrechi, TalitaPereira, Gustavo Jose da SilvaGazzinelli, Ricardo TostesVieira, Joseli LannesRodrigues, Maurício MartinsBortoluci, Karina RamalhoVasconcelos, José Ronnie Carvalho de2022-03-22T18:35:06Z2022-03-22T18:35:06Z2021MORASCHI, Barbara Ferri et al. Rapamycin Improves the Response of Effector and Memory CD8 + T Cells Induced by Immunization With ASP2 of Trypanosoma cruzi. Frontiers in Cellular and Infection Microbiology, v. 11, Article 676183, p. 1-16, 25 May 2021.2235-2988https://www.arca.fiocruz.br/handle/icict/5182210.3389/fcimb.2021.676183engFrontiers Media ASRapamycin Improves the Response of Effector and Memory CD8 + T Cells Induced by Immunization With ASP2 of Trypanosoma cruziinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleFederal University of São Paulo. Molecular Immunology Laboratory. Center of Molecular and Cellular Therapy. São Paulo, SP, Brazil / Federal University of São Paulo. Department of Microbiology, Immunology and Parasitology. São Paulo, SP, Brazil.Federal University of São Paulo. Molecular Immunology Laboratory. Center of Molecular and Cellular Therapy. São Paulo, SP, Brazil / Federal University of São Paulo. Department of Microbiology, Immunology and Parasitology. São Paulo, SP, Brazil.Federal University of São Paulo. Molecular Immunology Laboratory. Center of Molecular and Cellular Therapy. São Paulo, SP, Brazil / Federal University of São Paulo. Department of Microbiology, Immunology and Parasitology. São Paulo, SP, Brazil.Federal University of São Paulo. Recombinant Vaccines Laboratory. Department of Biosciences. Santos, SP, Brazil.Federal University of São Paulo. Recombinant Vaccines Laboratory. Department of Biosciences. Santos, SP, Brazil.Federal University of São Paulo. Molecular Immunology Laboratory. Center of Molecular and Cellular Therapy. São Paulo, SP, BrazilFederal University of São Paulo. Department of Pharmacology. São Paulo, SP, Brazil.Federal University of São Paulo. Department of Pharmacology. São Paulo, SP, Brazil.Oswaldo Cruz Foundation. René Rachou Institute. Belo Horizonte, MG, Brazil / University of Massachusetts Medical School. Division of Infectious Disease and Immunology. Department of Medicine. Worcester, MA, USA.Oswaldo Cruz Foundation. Oswaldo Cruz Institute. Laboratoy of Biology of the Interactions. Rio de Janeiro, RJ, Brazil.Federal University of São Paulo. Molecular Immunology Laboratory. Center of Molecular and Cellular Therapy. São Paulo, SP, Brazil / Federal University of São Paulo. Department of Microbiology, Immunology and Parasitology. São Paulo, SP, Brazil.Federal University of São Paulo. Molecular Immunology Laboratory. Center of Molecular and Cellular Therapy. São Paulo, SP, Brazil / Federal University of São Paulo. Department of Pharmacology. São Paulo, SP, Brazil.Federal University of São Paulo. Molecular Immunology Laboratory. Center of Molecular and Cellular Therapy. São Paulo, SP, Brazil / Federal University of São Paulo. Department of Microbiology, Immunology and Parasitology. São Paulo, SP, Brazil / Federal University of São Paulo. Recombinant Vaccines Laboratory. Department of Biosciences. Santos, SP, Brazil.Deficiency in memory formation and increased immunosenescence are pivotal features of Trypanosoma cruzi infection proposed to play a role in parasite persistence and disease development. The vaccination protocol that consists in a prime with plasmid DNA followed by the boost with a deficient recombinant human adenovirus type 5, both carrying the ASP2 gene of T. cruzi, is a powerful strategy to elicit effector memory CD8+ T-cells against this parasite. In virus infections, the inhibition of mTOR, a kinase involved in several biological processes, improves the response of memory CD8+ T-cells. Therefore, our aim was to assess the role of rapamycin, the pharmacological inhibitor of mTOR, in CD8+ T response against T. cruzi induced by heterologous prime-boost vaccine. For this purpose, C57BL/6 or A/Sn mice were immunized and daily treated with rapamycin for 34 days. CD8+ T-cells response was evaluated by immunophenotyping, intracellular staining, ELISpot assay and in vivo cytotoxicity. In comparison with vehicle-injection, rapamycin administration during immunization enhanced the frequency of ASP2-specific CD8+ T-cells and the percentage of the polyfunctional population, which degranulated (CD107a+) and secreted both interferon gamma (IFNγ) and tumor necrosis factor (TNF). The beneficial effects were long-lasting and could be detected 95 days after priming. Moreover, the effects were detected in mice immunized with ten-fold lower doses of plasmid/adenovirus. Additionally, the highly susceptible to T. cruzi infection A/Sn mice, when immunized with low vaccine doses, treated with rapamycin, and challenged with trypomastigote forms of the Y strain showed a survival rate of 100%, compared with 42% in vehicle-injected group. Trying to shed light on the biological mechanisms involved in these beneficial effects on CD8+ T-cells by mTOR inhibition after immunization, we showed that in vivo proliferation was higher after rapamycin treatment compared with vehicle-injected group. Taken together, our data provide a new approach to vaccine development against intracellular parasites, placing the mTOR inhibitor rapamycin as an adjuvant to improve effective CD8+ T-cell response.RapamycinmTORCD8+ T-cellsVaccineTrypanosoma cruziEffector CD8+ T cellsMemory CD8+ T cellsinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-83082https://www.arca.fiocruz.br/bitstream/icict/51822/1/license.txt9193a7c197bc67acd023525e72a03240MD51ORIGINALRapamycin Improves the Response of Effector.pdfRapamycin Improves the Response of Effector.pdfapplication/pdf8885984https://www.arca.fiocruz.br/bitstream/icict/51822/2/Rapamycin%20Improves%20the%20Response%20of%20Effector.pdfb0b6ff858b00649af5d4cb0a09efbf5fMD52icict/518222022-04-25 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| dc.title.pt_BR.fl_str_mv |
Rapamycin Improves the Response of Effector and Memory CD8 + T Cells Induced by Immunization With ASP2 of Trypanosoma cruzi |
| title |
Rapamycin Improves the Response of Effector and Memory CD8 + T Cells Induced by Immunization With ASP2 of Trypanosoma cruzi |
| spellingShingle |
Rapamycin Improves the Response of Effector and Memory CD8 + T Cells Induced by Immunization With ASP2 of Trypanosoma cruzi Moraschi, Barbara Ferri Rapamycin mTOR CD8+ T-cells Vaccine Trypanosoma cruzi Effector CD8+ T cells Memory CD8+ T cells |
| title_short |
Rapamycin Improves the Response of Effector and Memory CD8 + T Cells Induced by Immunization With ASP2 of Trypanosoma cruzi |
| title_full |
Rapamycin Improves the Response of Effector and Memory CD8 + T Cells Induced by Immunization With ASP2 of Trypanosoma cruzi |
| title_fullStr |
Rapamycin Improves the Response of Effector and Memory CD8 + T Cells Induced by Immunization With ASP2 of Trypanosoma cruzi |
| title_full_unstemmed |
Rapamycin Improves the Response of Effector and Memory CD8 + T Cells Induced by Immunization With ASP2 of Trypanosoma cruzi |
| title_sort |
Rapamycin Improves the Response of Effector and Memory CD8 + T Cells Induced by Immunization With ASP2 of Trypanosoma cruzi |
| author |
Moraschi, Barbara Ferri |
| author_facet |
Moraschi, Barbara Ferri Noronha, Isaú Henrique Ferreira, Camila Pontes Cariste, Leonardo Moro Monteiro, Caroline Brandão Denapoli, Priscila Vrechi, Talita Pereira, Gustavo Jose da Silva Gazzinelli, Ricardo Tostes Vieira, Joseli Lannes Rodrigues, Maurício Martins Bortoluci, Karina Ramalho Vasconcelos, José Ronnie Carvalho de |
| author_role |
author |
| author2 |
Noronha, Isaú Henrique Ferreira, Camila Pontes Cariste, Leonardo Moro Monteiro, Caroline Brandão Denapoli, Priscila Vrechi, Talita Pereira, Gustavo Jose da Silva Gazzinelli, Ricardo Tostes Vieira, Joseli Lannes Rodrigues, Maurício Martins Bortoluci, Karina Ramalho Vasconcelos, José Ronnie Carvalho de |
| author2_role |
author author author author author author author author author author author author |
| dc.contributor.author.fl_str_mv |
Moraschi, Barbara Ferri Noronha, Isaú Henrique Ferreira, Camila Pontes Cariste, Leonardo Moro Monteiro, Caroline Brandão Denapoli, Priscila Vrechi, Talita Pereira, Gustavo Jose da Silva Gazzinelli, Ricardo Tostes Vieira, Joseli Lannes Rodrigues, Maurício Martins Bortoluci, Karina Ramalho Vasconcelos, José Ronnie Carvalho de |
| dc.subject.en.pt_BR.fl_str_mv |
Rapamycin mTOR CD8+ T-cells Vaccine Trypanosoma cruzi Effector CD8+ T cells Memory CD8+ T cells |
| topic |
Rapamycin mTOR CD8+ T-cells Vaccine Trypanosoma cruzi Effector CD8+ T cells Memory CD8+ T cells |
| description |
Federal University of São Paulo. Molecular Immunology Laboratory. Center of Molecular and Cellular Therapy. São Paulo, SP, Brazil / Federal University of São Paulo. Department of Microbiology, Immunology and Parasitology. São Paulo, SP, Brazil. |
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2021 |
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2021 |
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2022-03-22T18:35:06Z |
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2022-03-22T18:35:06Z |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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article |
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MORASCHI, Barbara Ferri et al. Rapamycin Improves the Response of Effector and Memory CD8 + T Cells Induced by Immunization With ASP2 of Trypanosoma cruzi. Frontiers in Cellular and Infection Microbiology, v. 11, Article 676183, p. 1-16, 25 May 2021. |
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https://www.arca.fiocruz.br/handle/icict/51822 |
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2235-2988 |
| dc.identifier.doi.none.fl_str_mv |
10.3389/fcimb.2021.676183 |
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MORASCHI, Barbara Ferri et al. Rapamycin Improves the Response of Effector and Memory CD8 + T Cells Induced by Immunization With ASP2 of Trypanosoma cruzi. Frontiers in Cellular and Infection Microbiology, v. 11, Article 676183, p. 1-16, 25 May 2021. 2235-2988 10.3389/fcimb.2021.676183 |
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