Autophagic Induction Greatly Enhances Leishmania major Intracellular Survival Compared to Leishmania amazonensis in CBA/j-Infected Macrophages
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2018 |
| Outros Autores: | , , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Institucional da FIOCRUZ (ARCA) |
| Texto Completo: | https://www.arca.fiocruz.br/handle/icict/28956 |
Resumo: | Fundação de Amparo à Pesquisa do Estado da Bahia (PV http:// www.fapesb.ba.gov.br), Conselho Nacional de Pesquisa e Desenvolvimento Científico (PV http://www.cnpq.br) and National Institute of Science and Technology of Tropical (PV http://inct.cnpq.br/web/inct-dt). PV holds a grant from CNPq for productivity in research (307832/2015-5). |
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Dias, Beatriz Rocha SimõesSouza, Carina S deAlmeida, Niara de JesusLima, José Geraldo BomfimFukutani, Kiyoshi FerreiraSantos, Thiale Borges Silva dosCosta, Jaqueline FrançaBrodskyn, Claudia IdaMenezes, Juliana Perrone Bezerra deColombo, Maria IVeras, Patrícia Sampaio Tavares2018-09-20T18:38:18Z2018-09-20T18:38:18Z2018DIAS, B. R. S. et al. Autophagic Induction Greatly Enhances Leishmania major Intracellular Survival Compared to Leishmania amazonensis in CBA/j-Infected Macrophages. Frontiers in Microbiology, v. 9, aug. 2018.1664-302Xhttps://www.arca.fiocruz.br/handle/icict/2895610.3389/fmicb.2018.01890Fundação de Amparo à Pesquisa do Estado da Bahia (PV http:// www.fapesb.ba.gov.br), Conselho Nacional de Pesquisa e Desenvolvimento Científico (PV http://www.cnpq.br) and National Institute of Science and Technology of Tropical (PV http://inct.cnpq.br/web/inct-dt). PV holds a grant from CNPq for productivity in research (307832/2015-5).Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Interação Parasito-Hospedeiro e Epidemiologia. Salvador, BA, Brasil / Universidade Federal da Bahia. Escola de Medicina Veterinária e Zootecnia. Salvador, BA, Brasil / Instituto de Ciência e Tecnologia de Doenças Tropicais. Salvador, BA, BrasilFundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Interação Parasito-Hospedeiro e Epidemiologia. Salvador, BA, Brasil / Universidade Federal da Bahia. Escola de Medicina Veterinária e Zootecnia. Salvador, BA, Brasil / Instituto de Ciência e Tecnologia de Doenças Tropicais. Salvador, BA, BrasilFundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Interação Parasito-Hospedeiro e Epidemiologia. Salvador, BA, Brasil / Universidade Federal da Bahia. Escola de Medicina Veterinária e Zootecnia. Salvador, BA, Brasil / Instituto de Ciência e Tecnologia de Doenças Tropicais. Salvador, BA, BrasilFundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Interação Parasito-Hospedeiro e Epidemiologia. Salvador, BA, Brasil / Universidade Federal da Bahia. Escola de Medicina Veterinária e Zootecnia. Salvador, BA, Brasil / Instituto de Ciência e Tecnologia de Doenças Tropicais. Salvador, BA, BrasilFundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Inflamação e Biomarcadores. Salvador, BA, BrasilFundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Inflamação e Biomarcadores. Salvador, BA, BrasilFundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Inflamação e Biomarcadores. Salvador, BA, Brasil / Federal University of Bahia. Department of Biointeraction. Salvador, BA, BrasilFundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Interação Parasito-Hospedeiro e Epidemiologia. Salvador, BA, BrasilFundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Interação Parasito-Hospedeiro e Epidemiologia. Salvador, BA, BrasilNational University of Cuyo. Institute of Histology and Embryology. Laboratory of Cellular and Molecular Biology. Mendoza, ArgentinaFundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Inflamação e Biomarcadores. Salvador, BA, BrasilCBA mouse macrophages control Leishmania major infection yet are permissive to Leishmania amazonensis. Few studies have been conducted to assess the role played by autophagy in Leishmania infection. Therefore, we assessed whether the autophagic response of infected macrophages may account for the differential behavior of these two parasite strains. After 24 h of infection, the LC3-II/Act ratio increased in both L. amazonensis- and L. major-infected macrophages compared to uninfected controls, but less than in chloroquine-treated cells. This suggests that L. amazonensis and L. major activate autophagy in infected macrophages, without altering the autophagic flux. Furthermore, L. major-infected cells exhibited higher percentages of DQ-BSA-labeled parasitophorous vacuoles (50%) than those infected by L. amazonensis (25%). However, L. major- and L. amazonensis-induced parasitophorous vacuoles accumulated LysoTracker similarly, indicating that the acidity in both compartment was equivalent. At as early as 30 min, endogenous LC3 was recruited to both L. amazonensis- and L. major-induced parasitophorous vacuoles, while after 24 h a greater percentage of LC3 positive vacuoles was observed in L. amazonensis-infected cells (42.36%) compared to those infected by L. major (18.10%). Noteworthy, principal component analysis (PCA) and an hierarchical cluster analysis completely discriminated L. major-infected macrophages from L. amazonensis-infected cells accordingly to infection intensity and autophagic features of parasite-induced vacuoles. Then, we evaluated whether the modulation of autophagy exerted an influence on parasite infection in macrophages. No significant changes were observed in both infection rate or parasite load in macrophages treated with the autophagic inhibitors wortmannin, chloroquine or VPS34-IN1, as well as with the autophagic inducers rapamycin or physiological starvation, in comparison to untreated control cells. Interestingly, both autophagic inducers enhanced intracellular L. amazonensis and L. major viability, while the pharmacological inhibition of autophagy exerted no effects on intracellular parasite viability. We also demonstrated that autophagy induction reduced NO production by L. amazonensis- and L. major-infected macrophages but not alters arginase activity. These findings provide evidence that although L. amazonensis-induced parasitophorous vacuoles recruit LC3 more markedly, L. amazonensis and L. major similarly activate the autophagic pathway in CBA macrophages. Interestingly, the exogenous induction of autophagy favors L. major intracellular viability to a greater extent than L. amazonensis related to a reduction in the levels of NO.engFrontiers MediaLeishmaniaMacrófagosAutofagiaLC3Vacúolo parasitóforoLeishmaniaMacrophagesAutophagyLC3Parasitophorous vacuoleAutophagic Induction Greatly Enhances Leishmania major Intracellular Survival Compared to Leishmania amazonensis in CBA/j-Infected Macrophagesinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-82991https://www.arca.fiocruz.br/bitstream/icict/28956/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALDias BS Autophagic Induction Greatly Enhances ....pdfDias BS Autophagic Induction Greatly Enhances 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| dc.title.pt_BR.fl_str_mv |
Autophagic Induction Greatly Enhances Leishmania major Intracellular Survival Compared to Leishmania amazonensis in CBA/j-Infected Macrophages |
| title |
Autophagic Induction Greatly Enhances Leishmania major Intracellular Survival Compared to Leishmania amazonensis in CBA/j-Infected Macrophages |
| spellingShingle |
Autophagic Induction Greatly Enhances Leishmania major Intracellular Survival Compared to Leishmania amazonensis in CBA/j-Infected Macrophages Dias, Beatriz Rocha Simões Leishmania Macrófagos Autofagia LC3 Vacúolo parasitóforo Leishmania Macrophages Autophagy LC3 Parasitophorous vacuole |
| title_short |
Autophagic Induction Greatly Enhances Leishmania major Intracellular Survival Compared to Leishmania amazonensis in CBA/j-Infected Macrophages |
| title_full |
Autophagic Induction Greatly Enhances Leishmania major Intracellular Survival Compared to Leishmania amazonensis in CBA/j-Infected Macrophages |
| title_fullStr |
Autophagic Induction Greatly Enhances Leishmania major Intracellular Survival Compared to Leishmania amazonensis in CBA/j-Infected Macrophages |
| title_full_unstemmed |
Autophagic Induction Greatly Enhances Leishmania major Intracellular Survival Compared to Leishmania amazonensis in CBA/j-Infected Macrophages |
| title_sort |
Autophagic Induction Greatly Enhances Leishmania major Intracellular Survival Compared to Leishmania amazonensis in CBA/j-Infected Macrophages |
| author |
Dias, Beatriz Rocha Simões |
| author_facet |
Dias, Beatriz Rocha Simões Souza, Carina S de Almeida, Niara de Jesus Lima, José Geraldo Bomfim Fukutani, Kiyoshi Ferreira Santos, Thiale Borges Silva dos Costa, Jaqueline França Brodskyn, Claudia Ida Menezes, Juliana Perrone Bezerra de Colombo, Maria I Veras, Patrícia Sampaio Tavares |
| author_role |
author |
| author2 |
Souza, Carina S de Almeida, Niara de Jesus Lima, José Geraldo Bomfim Fukutani, Kiyoshi Ferreira Santos, Thiale Borges Silva dos Costa, Jaqueline França Brodskyn, Claudia Ida Menezes, Juliana Perrone Bezerra de Colombo, Maria I Veras, Patrícia Sampaio Tavares |
| author2_role |
author author author author author author author author author author |
| dc.contributor.author.fl_str_mv |
Dias, Beatriz Rocha Simões Souza, Carina S de Almeida, Niara de Jesus Lima, José Geraldo Bomfim Fukutani, Kiyoshi Ferreira Santos, Thiale Borges Silva dos Costa, Jaqueline França Brodskyn, Claudia Ida Menezes, Juliana Perrone Bezerra de Colombo, Maria I Veras, Patrícia Sampaio Tavares |
| dc.subject.other.pt_BR.fl_str_mv |
Leishmania Macrófagos Autofagia LC3 Vacúolo parasitóforo |
| topic |
Leishmania Macrófagos Autofagia LC3 Vacúolo parasitóforo Leishmania Macrophages Autophagy LC3 Parasitophorous vacuole |
| dc.subject.en.pt_BR.fl_str_mv |
Leishmania Macrophages Autophagy LC3 Parasitophorous vacuole |
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Fundação de Amparo à Pesquisa do Estado da Bahia (PV http:// www.fapesb.ba.gov.br), Conselho Nacional de Pesquisa e Desenvolvimento Científico (PV http://www.cnpq.br) and National Institute of Science and Technology of Tropical (PV http://inct.cnpq.br/web/inct-dt). PV holds a grant from CNPq for productivity in research (307832/2015-5). |
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2018 |
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2018-09-20T18:38:18Z |
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2018-09-20T18:38:18Z |
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2018 |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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DIAS, B. R. S. et al. Autophagic Induction Greatly Enhances Leishmania major Intracellular Survival Compared to Leishmania amazonensis in CBA/j-Infected Macrophages. Frontiers in Microbiology, v. 9, aug. 2018. |
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https://www.arca.fiocruz.br/handle/icict/28956 |
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1664-302X |
| dc.identifier.doi.none.fl_str_mv |
10.3389/fmicb.2018.01890 |
| identifier_str_mv |
DIAS, B. R. S. et al. Autophagic Induction Greatly Enhances Leishmania major Intracellular Survival Compared to Leishmania amazonensis in CBA/j-Infected Macrophages. Frontiers in Microbiology, v. 9, aug. 2018. 1664-302X 10.3389/fmicb.2018.01890 |
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eng |
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eng |
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Frontiers Media |
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Frontiers Media |
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