Trypanosoma cruzi Infection Induces Cellular Stress Response and Senescence-Like Phenotype in Murine Fibroblasts
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 start...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-07-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2018.01569/full |
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| author | Kamila Guimarães-Pinto Kamila Guimarães-Pinto Danielle Oliveira Nascimento Antonia Corrêa-Ferreira Antonia Corrêa-Ferreira Alexandre Morrot Alexandre Morrot Celio G. Freire-de-Lima Marcela F. Lopes George A. DosReis George A. DosReis Alessandra A. Filardy Alessandra A. Filardy |
| author_facet | Kamila Guimarães-Pinto Kamila Guimarães-Pinto Danielle Oliveira Nascimento Antonia Corrêa-Ferreira Antonia Corrêa-Ferreira Alexandre Morrot Alexandre Morrot Celio G. Freire-de-Lima Marcela F. Lopes George A. DosReis George A. DosReis Alessandra A. Filardy Alessandra A. Filardy |
| author_sort | Kamila Guimarães-Pinto |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-23T20:18:41Z |
| format | Article |
| id | doaj.art-82b98e6311864d19b8b48960e36e31d4 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-23T20:18:41Z |
| publishDate | 2018-07-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj.art-82b98e6311864d19b8b48960e36e31d42022-12-21T17:32:37ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-07-01910.3389/fimmu.2018.01569370562Trypanosoma cruzi Infection Induces Cellular Stress Response and Senescence-Like Phenotype in Murine FibroblastsKamila Guimarães-Pinto0Kamila Guimarães-Pinto1Danielle Oliveira Nascimento2Antonia Corrêa-Ferreira3Antonia Corrêa-Ferreira4Alexandre Morrot5Alexandre Morrot6Celio G. Freire-de-Lima7Marcela F. Lopes8George A. DosReis9George A. DosReis10Alessandra A. Filardy11Alessandra A. Filardy12Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, BrazilDepartamento de Imunologia, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, BrazilInstituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, BrazilInstituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, BrazilDepartamento de Imunologia, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, BrazilFaculdade de Medicina, Universidade Federal do Rio de Janeiro, Rio de Janeiro, BrazilLaboratório de Imunoparasitologia, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, BrazilInstituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, BrazilInstituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, BrazilInstituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, BrazilInstituto Nacional para Pesquisa Translacional em Saúde e Ambiente na Região Amazônica, Conselho Nacional de Desenvolvimento Científico e Tecnológico, Rio de Janeiro, BrazilInstituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, BrazilDepartamento de Imunologia, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, BrazilTrypanosoma 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.https://www.frontiersin.org/article/10.3389/fimmu.2018.01569/fullChagas diseaseTrypanosoma cruzisenescent-likesenescence-associated β-galactosidasesenescence-associated secretory phenotypereactive oxygen species |
| spellingShingle | Kamila Guimarães-Pinto Kamila Guimarães-Pinto Danielle Oliveira Nascimento Antonia Corrêa-Ferreira Antonia Corrêa-Ferreira Alexandre Morrot Alexandre Morrot Celio G. Freire-de-Lima Marcela F. Lopes George A. DosReis George A. DosReis Alessandra A. Filardy Alessandra A. Filardy Trypanosoma cruzi Infection Induces Cellular Stress Response and Senescence-Like Phenotype in Murine Fibroblasts Frontiers in Immunology Chagas disease Trypanosoma cruzi senescent-like senescence-associated β-galactosidase senescence-associated secretory phenotype reactive oxygen species |
| title | Trypanosoma cruzi Infection Induces Cellular Stress Response and Senescence-Like Phenotype in Murine Fibroblasts |
| title_full | Trypanosoma cruzi Infection Induces Cellular Stress Response and Senescence-Like Phenotype in Murine Fibroblasts |
| title_fullStr | Trypanosoma cruzi Infection Induces Cellular Stress Response and Senescence-Like Phenotype in Murine Fibroblasts |
| title_full_unstemmed | Trypanosoma cruzi Infection Induces Cellular Stress Response and Senescence-Like Phenotype in Murine Fibroblasts |
| title_short | Trypanosoma cruzi Infection Induces Cellular Stress Response and Senescence-Like Phenotype in Murine Fibroblasts |
| title_sort | trypanosoma cruzi infection induces cellular stress response and senescence like phenotype in murine fibroblasts |
| topic | Chagas disease Trypanosoma cruzi senescent-like senescence-associated β-galactosidase senescence-associated secretory phenotype reactive oxygen species |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2018.01569/full |
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