Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/31426
Title: Trypanosoma cruzi Infection Induces Cellular Stress Response and Senescence-Like Phenotype in Murine Fibroblasts
Authors: Pinto, Kamila Guimarães
Nascimento, Danielle Oliveira
Ferreira, Antonia Corrêa
Morrot, Alexandre
Lima, Celio G. Freire de
Lopes, Marcela F.
Reis, George A. dos
Filardy, Alessandra A.
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.
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 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.
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.
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 Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil.
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.
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.
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.
Keywords: Chagas Disease
Trypanosoma cruzi
Senescent-like
Senescence-associated β-galactosidase
Senescence-associated secretory phenotype
Reactive oxygen species
Deferoxamine
keywords: Doença de Chagas
Trypanosoma cruzi
Senescência
Espécies Reativas de Oxigênio
β-galactosidase associada à senescência
Fenótipo secretor associado à Senescência
Deferoxamine
DeCS: Espécies Reativas de Oxigênio
Issue Date: 2018
Publisher: Frontiers Media
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.
DOI: 10.3389/fimmu.2018.01569
ISSN: 1664-3224
Copyright: open access
Appears in Collections:IOC - Artigos de Periódicos

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