Autophagic Induction Greatly Enhances Leishmania major Intracellular Survival Compared to Leishmania amazonensis in CBA/j-Infected Macrophages

Detalhes bibliográficos
Autor(a) principal: Dias, Beatriz Rocha Simões
Data de Publicação: 2018
Outros Autores: 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
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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spelling 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
description 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).
publishDate 2018
dc.date.accessioned.fl_str_mv 2018-09-20T18:38:18Z
dc.date.available.fl_str_mv 2018-09-20T18:38:18Z
dc.date.issued.fl_str_mv 2018
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.citation.fl_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.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/28956
dc.identifier.issn.pt_BR.fl_str_mv 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
url https://www.arca.fiocruz.br/handle/icict/28956
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Frontiers Media
publisher.none.fl_str_mv Frontiers Media
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