Rapamycin Improves the Response of Effector and Memory CD8(+) T Cells Induced by Immunization With ASP2 of Trypanosoma cruzi

Detalhes bibliográficos
Autor(a) principal: Moraschi, Barbara Ferri
Data de Publicação: 2021
Outros Autores: Noronha, Isaú Henrique, Ferreira, Camila Pontes, Cariste, Leonardo M, Monteiro, Caroline B, Denapoli, Priscila, Vrechi, Talita, Pereira, Gustavo J S, Gazzinelli, Ricardo Tostes, Lannes-Vieira, Joseli, Rodrigues, Maurício M, Bortoluci, Karina R, Vasconcelos, José Ronnie C
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/55945
Resumo: Molecular Immunology Laboratory. Center of Molecular and Cellular Therapy. Federal University of São Paulo. São Paulo, SP, Brazil/Department of Microbiology. Immunology and Parasitology, Federal University of São Paulo. São Paulo, SP, Brazil.
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spelling Moraschi, Barbara FerriNoronha, Isaú HenriqueFerreira, Camila PontesCariste, Leonardo MMonteiro, Caroline BDenapoli, PriscilaVrechi, TalitaPereira, Gustavo J SGazzinelli, Ricardo TostesLannes-Vieira, JoseliRodrigues, Maurício MBortoluci, Karina RVasconcelos, José Ronnie C2022-12-14T19:20:56Z2022-12-14T19:20:56Z2021MORASCHI, Barbara Ferri et al. Rapamycin Improves the Response of Effector and Memory CD8+ T Cells Induced by Immunization With ASP2 of Trypanosoma cruzi. Front Cell Infect Microbiol., v. 11, 676183, 2021. doi: 10.3389/fcimb.2021.676183.2235-2988https://www.arca.fiocruz.br/handle/icict/55945engFrontiers 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/articleMolecular Immunology Laboratory. Center of Molecular and Cellular Therapy. Federal University of São Paulo. São Paulo, SP, Brazil/Department of Microbiology. Immunology and Parasitology, Federal University of São Paulo. São Paulo, SP, Brazil.Molecular Immunology Laboratory. Center of Molecular and Cellular Therapy. Federal University of São Paulo. São Paulo, SP, Brazil/Department of Microbiology. Immunology and Parasitology, Federal University of São Paulo. São Paulo, SP, Brazil.Molecular Immunology Laboratory. Center of Molecular and Cellular Therapy. Federal University of São Paulo. São Paulo, SP, Brazil/Department of Microbiology. Immunology and Parasitology, Federal University of São Paulo. São Paulo, SP, Brazil.Recombinant Vaccines Laboratory. Department of Biosciences. Federal University of São Paulo. Santos, SP, Brazil.Recombinant Vaccines Laboratory. Department of Biosciences. Federal University of São Paulo. Santos, SP, Brazil.Molecular Immunology Laboratory. Center of Molecular and Cellular Therapy. Federal University of São Paulo. São Paulo, SP, Brazil.Department of Pharmacology. Federal University of São Paulo. São Paulo, SP, Brazil.Department of Pharmacology. Federal University of São Paulo. São Paulo, SP, Brazil.René Rachou Institure. Oswaldo Cruz Foundation. Belo Horizonte, MG, Brazil/Division of Infectious Disease and Immunology. Department of Medicine. University of Massachusetts Medical School. Worcester, MA, United States.Laboratoy of Biology of the Interactions. Oswaldo Cruz Institute. Oswaldo Cruz Foundation. Rio de Janeiro, RJ, Brazil.Molecular Immunology Laboratory. Center of Molecular and Cellular Therapy. Federal University of São Paulo. São Paulo, SP, Brazil/Department of Microbiology. Immunology and Parasitology, Federal University of São Paulo. São Paulo, SP, Brazil.Molecular Immunology Laboratory. Center of Molecular and Cellular Therapy. Federal University of São Paulo. São Paulo, SP, Brazil/Department of Pharmacology. Federal University of São Paulo. São Paulo, SP, Brazil.Molecular Immunology Laboratory. Center of Molecular and Cellular Therapy. Federal University of São Paulo. São Paulo, SP, Brazil/Department of Microbiology. Immunology and Parasitology, Federal University of São Paulo. São Paulo, SP, Brazil/Recombinant Vaccines Laboratory. Department of Biosciences. Federal University of São Paulo. 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.CD8+ T-cellsTrypanosoma cruzieffector CD8+ T cellsmTORmemory CD8+ T cellsrapamycinvaccineinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-82991https://www.arca.fiocruz.br/bitstream/icict/55945/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALRapamycin Improves the Response of Effector and Memory CD8(+) T Cells Induced by Immunization With ASP2 of Trypanosoma cruzi.pdfRapamycin Improves the Response of Effector and Memory CD8(+) T Cells Induced by Immunization With ASP2 of Trypanosoma cruzi.pdfapplication/pdf5796983https://www.arca.fiocruz.br/bitstream/icict/55945/2/Rapamycin%20Improves%20the%20Response%20of%20Effector%20and%20Memory%20CD8%28%2b%29%20T%20Cells%20Induced%20by%20Immunization%20With%20ASP2%20of%20Trypanosoma%20cruzi.pdfa297d1ec2bf5a9910103b90cae9866acMD52icict/559452022-12-14 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dc.title.en_US.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
CD8+ T-cells
Trypanosoma cruzi
effector CD8+ T cells
mTOR
memory CD8+ T cells
rapamycin
vaccine
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 M
Monteiro, Caroline B
Denapoli, Priscila
Vrechi, Talita
Pereira, Gustavo J S
Gazzinelli, Ricardo Tostes
Lannes-Vieira, Joseli
Rodrigues, Maurício M
Bortoluci, Karina R
Vasconcelos, José Ronnie C
author_role author
author2 Noronha, Isaú Henrique
Ferreira, Camila Pontes
Cariste, Leonardo M
Monteiro, Caroline B
Denapoli, Priscila
Vrechi, Talita
Pereira, Gustavo J S
Gazzinelli, Ricardo Tostes
Lannes-Vieira, Joseli
Rodrigues, Maurício M
Bortoluci, Karina R
Vasconcelos, José Ronnie C
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 M
Monteiro, Caroline B
Denapoli, Priscila
Vrechi, Talita
Pereira, Gustavo J S
Gazzinelli, Ricardo Tostes
Lannes-Vieira, Joseli
Rodrigues, Maurício M
Bortoluci, Karina R
Vasconcelos, José Ronnie C
dc.subject.en.en_US.fl_str_mv CD8+ T-cells
Trypanosoma cruzi
effector CD8+ T cells
mTOR
memory CD8+ T cells
rapamycin
vaccine
topic CD8+ T-cells
Trypanosoma cruzi
effector CD8+ T cells
mTOR
memory CD8+ T cells
rapamycin
vaccine
description Molecular Immunology Laboratory. Center of Molecular and Cellular Therapy. Federal University of São Paulo. São Paulo, SP, Brazil/Department of Microbiology. Immunology and Parasitology, Federal University of São Paulo. São Paulo, SP, Brazil.
publishDate 2021
dc.date.issued.fl_str_mv 2021
dc.date.accessioned.fl_str_mv 2022-12-14T19:20:56Z
dc.date.available.fl_str_mv 2022-12-14T19:20:56Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.citation.fl_str_mv MORASCHI, Barbara Ferri et al. Rapamycin Improves the Response of Effector and Memory CD8+ T Cells Induced by Immunization With ASP2 of Trypanosoma cruzi. Front Cell Infect Microbiol., v. 11, 676183, 2021. doi: 10.3389/fcimb.2021.676183.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/55945
dc.identifier.issn.en_US.fl_str_mv 2235-2988
identifier_str_mv MORASCHI, Barbara Ferri et al. Rapamycin Improves the Response of Effector and Memory CD8+ T Cells Induced by Immunization With ASP2 of Trypanosoma cruzi. Front Cell Infect Microbiol., v. 11, 676183, 2021. doi: 10.3389/fcimb.2021.676183.
2235-2988
url https://www.arca.fiocruz.br/handle/icict/55945
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Frontiers Media AS
publisher.none.fl_str_mv Frontiers Media AS
dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
instname:Fundação Oswaldo Cruz (FIOCRUZ)
instacron:FIOCRUZ
instname_str Fundação Oswaldo Cruz (FIOCRUZ)
instacron_str FIOCRUZ
institution FIOCRUZ
reponame_str Repositório Institucional da FIOCRUZ (ARCA)
collection Repositório Institucional da FIOCRUZ (ARCA)
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