Author | Moraschi, Barbara Ferri | |
Author | Noronha, Isaú Henrique | |
Author | Ferreira, Camila Pontes | |
Author | Cariste, Leonardo M. | |
Author | Monteiro, Caroline B. | |
Author | Denapoli, Priscila | |
Author | Vrechi, Talita | |
Author | Pereira, Gustavo J. S. | |
Author | Gazinelli, Ricardo T. | |
Author | Lannes-Vieira, Joseli | |
Author | Rodrigues, Mauricio M. | |
Author | Bortoluci, Karina R. | |
Author | Vasconcelos, José Ronnie C. | |
Access date | 2021-07-08T15:18:12Z | |
Available date | 2021-07-08T15:18:12Z | |
Document date | 2021 | |
Citation | 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, Article 676183, 16 p, May 2021. | pt_BR |
ISSN | 2235-2988 | pt_BR |
URI | https://www.arca.fiocruz.br/handle/icict/48069 | |
Language | eng | pt_BR |
Publisher | Frontiers Media | pt_BR |
Rights | open access | pt_BR |
Subject in Portuguese | Rapamicina | pt_BR |
Subject in Portuguese | Vacina | pt_BR |
Subject in Portuguese | Trypanosoma cruzi | pt_BR |
Subject in Portuguese | Células T CD8+ | pt_BR |
Subject in Portuguese | mTOR | pt_BR |
Subject in Portuguese | Célula T Effector CD8+ | pt_BR |
Subject in Portuguese | Memória CD8+ células T | pt_BR |
Title | Rapamycin Improves the Response of Effector and Memory CD8+ T Cells Induced by Immunization With ASP2 of Trypanosoma cruzi | pt_BR |
Type | Article | pt_BR |
DOI | 10.3389/fcimb.2021.676183 | |
Abstract | 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 (IFNg) 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. | pt_BR |
Affilliation | Universidade Federal de São Paulo. Centro de Terapia Molecular e Celular. Laboratório de Imunologia Molecular. São Paulo, SP, Brasil / Universidade Federal de São Paulo. Departamento de Microbiologia, Imunologia e Parasitologia. São Paulo, SP, Brasil. | pt_BR |
Affilliation | Universidade Federal de São Paulo. Centro de Terapia Molecular e Celular. Laboratório de Imunologia Molecular. São Paulo, SP, Brasil / Universidade Federal de São Paulo. Departamento de Microbiologia, Imunologia e Parasitologia. São Paulo, SP, Brasil. | pt_BR |
Affilliation | Universidade Federal de São Paulo. Centro de Terapia Molecular e Celular. Laboratório de Imunologia Molecular. São Paulo, SP, Brasil / Universidade Federal de São Paulo. Departamento de Microbiologia, Imunologia e Parasitologia. São Paulo, SP, Brasil. | pt_BR |
Affilliation | Universidade Federal de São Paulo. Departamento de Biociências. Laboratório de Vacinas Recombinantes. Santos, SP, Brasil. | pt_BR |
Affilliation | Universidade Federal de São Paulo. Departamento de Biociências. Laboratório de Vacinas Recombinantes. Santos, SP, Brasil. | pt_BR |
Affilliation | Universidade Federal de São Paulo. Centro de Terapia Molecular e Celular. Laboratório de Imunologia Molecular. São Paulo, SP, Brasil. | pt_BR |
Affilliation | Universidade Federal de São Paulo. Departamento de Farmacologia. S]ao Paulo, SP, Brasil. | pt_BR |
Affilliation | Universidade Federal de São Paulo. Departamento de Farmacologia. S]ao Paulo, SP, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, Brasil / University of Massachusetts Medical School. Department of Medicine. Division of Infectious Disease and Immunology. Worcester, MA, USA. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia das Interações. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Universidade Federal de São Paulo. Centro de Terapia Molecular e Celular. Laboratório de Imunologia Molecular. São Paulo, SP, Brasil / Universidade Federal de São Paulo. Departamento de Microbiologia, Imunologia e Parasitologia. São Paulo, SP, Brasil. | pt_BR |
Affilliation | Universidade Federal de São Paulo. Centro de Terapia Molecular e Celular. Laboratório de Imunologia Molecular. São Paulo, SP, Brasil / Universidade Federal de São Paulo. Departamento de Farmacologia. S]ao Paulo, SP, Brasil. | pt_BR |
Affilliation | Universidade Federal de São Paulo. Centro de Terapia Molecular e Celular. Laboratório de Imunologia Molecular. São Paulo, SP, Brasil / Universidade Federal de São Paulo. Departamento de Microbiologia, Imunologia e Parasitologia. São Paulo, SP, Brasil / Universidade Federal de São Paulo. Departamento de Biociências. Laboratório de Vacinas Recombinantes. Santos, SP, Brasil. | pt_BR |
Subject | Rapamycin | pt_BR |
Subject | mTOR | pt_BR |
Subject | CD8+ T-cells | pt_BR |
Subject | Vaccine | pt_BR |
Subject | Trypanosoma cruzi | pt_BR |
Subject | Effector CD8+ T cell | pt_BR |
Subject | Memory CD8+ T cells | pt_BR |