Author | Pinto, Kamila Guimarães | |
Author | Nascimento, Danielle Oliveira | |
Author | Ferreira, Antonia Corrêa | |
Author | Morrot, Alexandre | |
Author | Lima, Celio G. Freire de | |
Author | Lopes, Marcela F. | |
Author | Reis, George A. dos | |
Author | Filardy, Alessandra A. | |
Access date | 2019-02-05T14:36:28Z | |
Available date | 2019-02-05T14:36:28Z | |
Document date | 2018 | |
Citation | PINTO, Kamila Guimarães et al. Trypanosoma cruzi infection induces cellular stress response and senescence-like Phenotype in Murine Fibroblasts. Frontiers in Immunology, v. 9, p. 1-11, July 2018. | pt_BR |
ISSN | 1664-3224 | pt_BR |
URI | https://www.arca.fiocruz.br/handle/icict/31426 | |
Language | eng | pt_BR |
Publisher | Frontiers Media | pt_BR |
Rights | open access | |
Subject in Portuguese | Doença de Chagas | pt_BR |
Subject in Portuguese | Trypanosoma cruzi | pt_BR |
Subject in Portuguese | Senescência | pt_BR |
Subject in Portuguese | Espécies Reativas de Oxigênio | pt_BR |
Subject in Portuguese | β-galactosidase associada à senescência | pt_BR |
Subject in Portuguese | Fenótipo secretor associado à Senescência | pt_BR |
Subject in Portuguese | Deferoxamine | pt_BR |
Title | Trypanosoma cruzi Infection Induces Cellular Stress Response and Senescence-Like Phenotype in Murine Fibroblasts | pt_BR |
Type | Article | |
DOI | 10.3389/fimmu.2018.01569 | |
Abstract | Trypanosoma cruzi infects and replicates within a wide variety of immune and non-immune cells. Here, we investigated early cellular responses induced in NIH-3T3 fibroblasts upon infection with trypomastigote forms of T. cruzi. We show that fibroblasts were susceptible to T. cruzi infection and started to release trypomastigotes to the culture medium after 4 days of infection. Also, we found that T. cruzi infection reduced the number of fibroblasts in 3-day cell cultures, by altering fibroblast proliferation. Infected fibroblasts displayed distinctive phenotypic alterations, including enlarged and flattened morphology with a nuclei accumulation of senescence-associated heterochromatin foci. In addition, infection induced an overexpression of the enzyme senescence-associated β-galactosidase (SA-β-gal), an activation marker of the cellular senescence program, as well as the production of cytokines and chemokines involved with the senescence-associated secretory phenotype (SASP) such as IL-6, TNF-α, IL-1β, and MCP-1. Infected fibroblasts released increased amounts of stress-associated factors nitric oxide (NO) and reactive oxygen species (ROS), and the treatment with antioxidants deferoxamine (DFO) and N-acetylcysteine reduced ROS generation, secretion of SASP-related cytokine IL-6, SA-β-gal activity, and parasite load by infected fibroblasts. Taken together, our data suggest that T. cruzi infection triggers a rapid cellular stress response followed by induction of a senescent-like phenotype in NIH-3T3 fibroblasts, enabling them to act as reservoirs of parasites during the early stages of the Chagas disease. | pt_BR |
Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil / Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Góes. Departamento de Imunologia. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil / Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Góes. Departamento de Imunologia. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Universidade Federal do Rio de Janeiro. Faculdade de Medicina. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunoparasitologia. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil / Instituto Nacional para Pesquisa Translacional em Saúde e Ambiente na Região Amazônica. Conselho Nacional de Desenvolvimento Científico e Tecnológico. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil / Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Góes. Departamento de Imunologia. Rio de Janeiro, RJ, Brasil. | pt_BR |
Subject | Chagas Disease | pt_BR |
Subject | Trypanosoma cruzi | pt_BR |
Subject | Senescent-like | pt_BR |
Subject | Senescence-associated β-galactosidase | pt_BR |
Subject | Senescence-associated secretory phenotype | pt_BR |
Subject | Reactive oxygen species | pt_BR |
Subject | Deferoxamine | pt_BR |
DeCS | Espécies Reativas de Oxigênio | pt_BR |
xmlui.metadata.dc.subject.ods | 03 Saúde e Bem-Estar | |