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
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/92610
Ver los metadatos del registro completo
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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 |
_version_ |
1844613565999218688 |
score |
13.070432 |