Autophagic induction Greatly Enhances Leishmania major intracellular survival compared to Leishmania amazonensis in CBA/j-infected macrophages

Autores
Dias, Beatriz R. S.; de Souza, Carina S.; Almeida, Niara de Jesus; Lima, José G. B.; Fukutani, Kiyoshi F.; dos Santos, Thiale B. S.; França Cost, Jaqueline; Brodskyn, Claudia I.; de Menezes, Juliana P. B.; Colombo, Maria Isabel; Veras, Patricia S. T.
Año de publicación
2018
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
CBA 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.
Fil: Dias, Beatriz R.S.. Gonçalo Moniz Institute;
Fil: de Souza, Carina S.. Gonçalo Moniz Institute;
Fil: Almeida, Niara de Jesus. Gonçalo Moniz Institute;
Fil: Lima, José G.B.. Gonçalo Moniz Institute;
Fil: Fukutani, Kiyoshi F.. Gonçalo Moniz Institute;
Fil: dos Santos, Thiale B.S.. Gonçalo Moniz Institute;
Fil: França-Cost, Jaqueline. Universidade Federal da Bahia; Brasil. Gonçalo Moniz Institute;
Fil: Brodskyn, Claudia I.. Gonçalo Moniz Institute;
Fil: de Menezes, Juliana P.B.. Gonçalo Moniz Institute;
Fil: Colombo, Maria Isabel. Universidad Nacional de Cuyo; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina
Fil: Veras, Patricia S.T.. Gonçalo Moniz Institute;
Materia
AUTOPHAGY
LC3
LEISHMANIA
MACROPHAGES
PARASITOPHOROUS VACUOLE
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/92610

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network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Autophagic induction Greatly Enhances Leishmania major intracellular survival compared to Leishmania amazonensis in CBA/j-infected macrophagesDias, Beatriz R. S.de Souza, Carina S.Almeida, Niara de JesusLima, José G. B.Fukutani, Kiyoshi F.dos Santos, Thiale B. S.França Cost, JaquelineBrodskyn, Claudia I.de Menezes, Juliana P. B.Colombo, Maria IsabelVeras, Patricia S. T.AUTOPHAGYLC3LEISHMANIAMACROPHAGESPARASITOPHOROUS VACUOLEhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1CBA 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.Fil: Dias, Beatriz R.S.. Gonçalo Moniz Institute;Fil: de Souza, Carina S.. Gonçalo Moniz Institute;Fil: Almeida, Niara de Jesus. Gonçalo Moniz Institute;Fil: Lima, José G.B.. Gonçalo Moniz Institute;Fil: Fukutani, Kiyoshi F.. Gonçalo Moniz Institute;Fil: dos Santos, Thiale B.S.. Gonçalo Moniz Institute;Fil: França-Cost, Jaqueline. Universidade Federal da Bahia; Brasil. Gonçalo Moniz Institute;Fil: Brodskyn, Claudia I.. Gonçalo Moniz Institute;Fil: de Menezes, Juliana P.B.. Gonçalo Moniz Institute;Fil: Colombo, Maria Isabel. Universidad Nacional de Cuyo; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Veras, Patricia S.T.. Gonçalo Moniz Institute;Frontiers Research Foundation2018-08info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/92610Dias, Beatriz R. S.; de Souza, Carina S.; Almeida, Niara de Jesus; Lima, José G. B.; Fukutani, Kiyoshi F.; et al.; Autophagic induction Greatly Enhances Leishmania major intracellular survival compared to Leishmania amazonensis in CBA/j-infected macrophages; Frontiers Research Foundation; Frontiers in Microbiology; 9; AUG; 8-2018; 1-151664-302XCONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.3389/fmicb.2018.01890info:eu-repo/semantics/altIdentifier/url/https://www.frontiersin.org/articles/10.3389/fmicb.2018.01890/fullinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:50:49Zoai:ri.conicet.gov.ar:11336/92610instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 09:50:49.708CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.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 R. S.
AUTOPHAGY
LC3
LEISHMANIA
MACROPHAGES
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
dc.creator.none.fl_str_mv Dias, Beatriz R. S.
de Souza, Carina S.
Almeida, Niara de Jesus
Lima, José G. B.
Fukutani, Kiyoshi F.
dos Santos, Thiale B. S.
França Cost, Jaqueline
Brodskyn, Claudia I.
de Menezes, Juliana P. B.
Colombo, Maria Isabel
Veras, Patricia S. T.
author Dias, Beatriz R. S.
author_facet Dias, Beatriz R. S.
de Souza, Carina S.
Almeida, Niara de Jesus
Lima, José G. B.
Fukutani, Kiyoshi F.
dos Santos, Thiale B. S.
França Cost, Jaqueline
Brodskyn, Claudia I.
de Menezes, Juliana P. B.
Colombo, Maria Isabel
Veras, Patricia S. T.
author_role author
author2 de Souza, Carina S.
Almeida, Niara de Jesus
Lima, José G. B.
Fukutani, Kiyoshi F.
dos Santos, Thiale B. S.
França Cost, Jaqueline
Brodskyn, Claudia I.
de Menezes, Juliana P. B.
Colombo, Maria Isabel
Veras, Patricia S. T.
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv AUTOPHAGY
LC3
LEISHMANIA
MACROPHAGES
PARASITOPHOROUS VACUOLE
topic AUTOPHAGY
LC3
LEISHMANIA
MACROPHAGES
PARASITOPHOROUS VACUOLE
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv CBA 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.
Fil: Dias, Beatriz R.S.. Gonçalo Moniz Institute;
Fil: de Souza, Carina S.. Gonçalo Moniz Institute;
Fil: Almeida, Niara de Jesus. Gonçalo Moniz Institute;
Fil: Lima, José G.B.. Gonçalo Moniz Institute;
Fil: Fukutani, Kiyoshi F.. Gonçalo Moniz Institute;
Fil: dos Santos, Thiale B.S.. Gonçalo Moniz Institute;
Fil: França-Cost, Jaqueline. Universidade Federal da Bahia; Brasil. Gonçalo Moniz Institute;
Fil: Brodskyn, Claudia I.. Gonçalo Moniz Institute;
Fil: de Menezes, Juliana P.B.. Gonçalo Moniz Institute;
Fil: Colombo, Maria Isabel. Universidad Nacional de Cuyo; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina
Fil: Veras, Patricia S.T.. Gonçalo Moniz Institute;
description CBA 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.
publishDate 2018
dc.date.none.fl_str_mv 2018-08
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/92610
Dias, Beatriz R. S.; de Souza, Carina S.; Almeida, Niara de Jesus; Lima, José G. B.; Fukutani, Kiyoshi F.; et al.; Autophagic induction Greatly Enhances Leishmania major intracellular survival compared to Leishmania amazonensis in CBA/j-infected macrophages; Frontiers Research Foundation; Frontiers in Microbiology; 9; AUG; 8-2018; 1-15
1664-302X
CONICET Digital
CONICET
url http://hdl.handle.net/11336/92610
identifier_str_mv Dias, Beatriz R. S.; de Souza, Carina S.; Almeida, Niara de Jesus; Lima, José G. B.; Fukutani, Kiyoshi F.; et al.; Autophagic induction Greatly Enhances Leishmania major intracellular survival compared to Leishmania amazonensis in CBA/j-infected macrophages; Frontiers Research Foundation; Frontiers in Microbiology; 9; AUG; 8-2018; 1-15
1664-302X
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.3389/fmicb.2018.01890
info:eu-repo/semantics/altIdentifier/url/https://www.frontiersin.org/articles/10.3389/fmicb.2018.01890/full
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Frontiers Research Foundation
publisher.none.fl_str_mv Frontiers Research Foundation
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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