| 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 | Gazzinelli, Ricardo Tostes | |
| Author | Lannes-Vieira, Joseli | |
| Author | Rodrigues, Maurício M | |
| Author | Bortoluci, Karina R | |
| Author | Vasconcelos, José Ronnie C | |
| Access date | 2022-12-14T19:20:56Z | |
| Available date | 2022-12-14T19:20:56Z | |
| 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, 676183, 2021. doi: 10.3389/fcimb.2021.676183. | en_US |
| ISSN | 2235-2988 | en_US |
| URI | https://www.arca.fiocruz.br/handle/icict/55945 | |
| Language | eng | en_US |
| Publisher | Frontiers Media AS | en_US |
| Rights | open access | en_US |
| Title | Rapamycin Improves the Response of Effector and Memory CD8(+) T Cells Induced by Immunization With ASP2 of Trypanosoma cruzi | en_US |
| Type | Article | en_US |
| 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 (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. | en_US |
| Affilliation | 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. | en_US |
| Affilliation | 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. | en_US |
| Affilliation | 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. | en_US |
| Affilliation | Recombinant Vaccines Laboratory. Department of Biosciences. Federal University of São Paulo. Santos, SP, Brazil. | en_US |
| Affilliation | Recombinant Vaccines Laboratory. Department of Biosciences. Federal University of São Paulo. Santos, SP, Brazil. | en_US |
| Affilliation | Molecular Immunology Laboratory. Center of Molecular and Cellular Therapy. Federal University of São Paulo. São Paulo, SP, Brazil. | en_US |
| Affilliation | Department of Pharmacology. Federal University of São Paulo. São Paulo, SP, Brazil. | en_US |
| Affilliation | Department of Pharmacology. Federal University of São Paulo. São Paulo, SP, Brazil. | en_US |
| Affilliation | 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. | en_US |
| Affilliation | Laboratoy of Biology of the Interactions. Oswaldo Cruz Institute. Oswaldo Cruz Foundation. Rio de Janeiro, RJ, Brazil. | en_US |
| Affilliation | 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. | en_US |
| Affilliation | 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. | en_US |
| Affilliation | 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. | en_US |
| Subject | CD8+ T-cells | en_US |
| Subject | Trypanosoma cruzi | en_US |
| Subject | effector CD8+ T cells | en_US |
| Subject | mTOR | en_US |
| Subject | memory CD8+ T cells | en_US |
| Subject | rapamycin | en_US |
| Subject | vaccine | en_US |
| xmlui.metadata.dc.subject.ods | 03 Saúde e Bem-Estar | |
