The BtaF Adhesin Is Necessary for Full Virulence During Respiratory Infection by Brucella suis and Is a Novel Immunogen for Nasal Vaccination Against Brucella Infection

Autores
Muñoz González, Florencia; Sycz, Gabriela; Alonso Paiva, Iván Mathias; Linke, Dirk; Zorreguieta, Ángeles; Baldi, Pablo Cesar; Ferrero, Mariana Cristina
Año de publicación
2019
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Brucella enters their hosts mostly through mucosae from where it spreads systemically.Adhesion to extracellular matrix (ECM) components or to host cells is important for theinfectious process, and is mediated by several adhesins, including the BtaF trimericautotransporter. Although Th1 responses and gamma interferon (IFN-g) are important forprotection, antibodies able to block adhesions might also contribute to prevent Brucellainfection. We evaluated the importance of BtaF for respiratory Brucella infection, andcharacterized the immune response and protection from mucosal challenge induced bynasal vaccination with recombinant BtaF. While lung CFU numbers did not differ at day1 p.i. between mice intratracheally inoculated with B. suis M1330 (wild type) and thosereceiving a 1btaF mutant, they were reduced in the latter group at 7 and 30 days p.i.For vaccination studies the BtaF passenger domain was engineered and expressed asa soluble trimeric protein. Mice were immunized by the nasal route with BtaF or saline(control group) plus the mucosal adjuvant c-di-AMP. Specific anti-BtaF antibodies (IgGand IgA) were increased in serum, including a mixed IgG2a/IgG1 response. In vitro,these antibodies reduced bacterial adhesion to A549 alveolar epithelial cells. Specific IgAantibodies were also increased in several mucosae. Spleen cells from BtaF immunizedmice significantly increased their IL-2, IL-5, IL-17, and IFN-g secretion upon antigenstimulation. In cervical draining lymph nodes, antigen-experienced CD4+ T cells weremaintained mainly as central memory cells. A BtaF-specific delayed-type hypersensitivityresponse was detected in BtaF immunized mice. Lung cells from the latter producedhigh levels of IFN-g upon antigen stimulation. Although nasal immunization with BtaF didnot protect mice against B. suis respiratory challenge, it conferred significant protectionfrom intragastric challenge; the splenic load of B. suis was reduced by 3.28 log CFU inimmunized mice. This study shows that nasal vaccination with BtaF+c-di-AMP protectsagainst intragastric challenge with B. suis by inducing local and systemic antibodyresponses, central memory CD4+ T cells and strong Th1 responses. Therefore, althoughBtaF vaccination did not protect fromB. suis respiratory infection, this adhesin constitutesa promising immunogen against mucosal B. suis infection.
Fil: Muñoz González, Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; Argentina
Fil: Sycz, Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Fil: Alonso Paiva, Iván Mathias. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; Argentina
Fil: Linke, Dirk. Centro de Síntesis Ecológica y Evolutiva, Universidad de Oslo; Noruega
Fil: Zorreguieta, Ángeles. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Fil: Baldi, Pablo Cesar. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; Argentina
Fil: Ferrero, Mariana Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; Argentina
Materia
BACTERIAL ADHESINS
BRUCELLA SUIS
BTAF AUTOTRANSPORTER
INTRAGASTRIC CHALLENGE
MUCOSAL IMMUNITY
NASAL IMMUNIZATION
RESPIRATORY INFECTION
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:11336/121073
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/121073
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling The BtaF Adhesin Is Necessary for Full Virulence During Respiratory Infection by Brucella suis and Is a Novel Immunogen for Nasal Vaccination Against Brucella InfectionMuñoz González, FlorenciaSycz, GabrielaAlonso Paiva, Iván MathiasLinke, DirkZorreguieta, ÁngelesBaldi, Pablo CesarFerrero, Mariana CristinaBACTERIAL ADHESINSBRUCELLA SUISBTAF AUTOTRANSPORTERINTRAGASTRIC CHALLENGEMUCOSAL IMMUNITYNASAL IMMUNIZATIONRESPIRATORY INFECTIONhttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3Brucella enters their hosts mostly through mucosae from where it spreads systemically.Adhesion to extracellular matrix (ECM) components or to host cells is important for theinfectious process, and is mediated by several adhesins, including the BtaF trimericautotransporter. Although Th1 responses and gamma interferon (IFN-g) are important forprotection, antibodies able to block adhesions might also contribute to prevent Brucellainfection. We evaluated the importance of BtaF for respiratory Brucella infection, andcharacterized the immune response and protection from mucosal challenge induced bynasal vaccination with recombinant BtaF. While lung CFU numbers did not differ at day1 p.i. between mice intratracheally inoculated with B. suis M1330 (wild type) and thosereceiving a 1btaF mutant, they were reduced in the latter group at 7 and 30 days p.i.For vaccination studies the BtaF passenger domain was engineered and expressed asa soluble trimeric protein. Mice were immunized by the nasal route with BtaF or saline(control group) plus the mucosal adjuvant c-di-AMP. Specific anti-BtaF antibodies (IgGand IgA) were increased in serum, including a mixed IgG2a/IgG1 response. In vitro,these antibodies reduced bacterial adhesion to A549 alveolar epithelial cells. Specific IgAantibodies were also increased in several mucosae. Spleen cells from BtaF immunizedmice significantly increased their IL-2, IL-5, IL-17, and IFN-g secretion upon antigenstimulation. In cervical draining lymph nodes, antigen-experienced CD4+ T cells weremaintained mainly as central memory cells. A BtaF-specific delayed-type hypersensitivityresponse was detected in BtaF immunized mice. Lung cells from the latter producedhigh levels of IFN-g upon antigen stimulation. Although nasal immunization with BtaF didnot protect mice against B. suis respiratory challenge, it conferred significant protectionfrom intragastric challenge; the splenic load of B. suis was reduced by 3.28 log CFU inimmunized mice. This study shows that nasal vaccination with BtaF+c-di-AMP protectsagainst intragastric challenge with B. suis by inducing local and systemic antibodyresponses, central memory CD4+ T cells and strong Th1 responses. Therefore, althoughBtaF vaccination did not protect fromB. suis respiratory infection, this adhesin constitutesa promising immunogen against mucosal B. suis infection.Fil: Muñoz González, Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; ArgentinaFil: Sycz, Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Alonso Paiva, Iván Mathias. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; ArgentinaFil: Linke, Dirk. Centro de Síntesis Ecológica y Evolutiva, Universidad de Oslo; NoruegaFil: Zorreguieta, Ángeles. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Baldi, Pablo Cesar. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; ArgentinaFil: Ferrero, Mariana Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; ArgentinaFrontiers Media S.A.2019-07-26info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/121073Muñoz González, Florencia; Sycz, Gabriela; Alonso Paiva, Iván Mathias; Linke, Dirk; Zorreguieta, Ángeles; et al.; The BtaF Adhesin Is Necessary for Full Virulence During Respiratory Infection by Brucella suis and Is a Novel Immunogen for Nasal Vaccination Against Brucella Infection; Frontiers Media S.A.; Frontiers in immunology; 10; 1775; 26-7-2019; 1-161664-3224CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.frontiersin.org/article/10.3389/fimmu.2019.01775/fullinfo:eu-repo/semantics/altIdentifier/doi/10.3389/fimmu.2019.01775info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:36:47Zoai:ri.conicet.gov.ar:11336/121073instacron: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 10:36:47.361CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv The BtaF Adhesin Is Necessary for Full Virulence During Respiratory Infection by Brucella suis and Is a Novel Immunogen for Nasal Vaccination Against Brucella Infection
title The BtaF Adhesin Is Necessary for Full Virulence During Respiratory Infection by Brucella suis and Is a Novel Immunogen for Nasal Vaccination Against Brucella Infection
spellingShingle The BtaF Adhesin Is Necessary for Full Virulence During Respiratory Infection by Brucella suis and Is a Novel Immunogen for Nasal Vaccination Against Brucella Infection
Muñoz González, Florencia
BACTERIAL ADHESINS
BRUCELLA SUIS
BTAF AUTOTRANSPORTER
INTRAGASTRIC CHALLENGE
MUCOSAL IMMUNITY
NASAL IMMUNIZATION
RESPIRATORY INFECTION
title_short The BtaF Adhesin Is Necessary for Full Virulence During Respiratory Infection by Brucella suis and Is a Novel Immunogen for Nasal Vaccination Against Brucella Infection
title_full The BtaF Adhesin Is Necessary for Full Virulence During Respiratory Infection by Brucella suis and Is a Novel Immunogen for Nasal Vaccination Against Brucella Infection
title_fullStr The BtaF Adhesin Is Necessary for Full Virulence During Respiratory Infection by Brucella suis and Is a Novel Immunogen for Nasal Vaccination Against Brucella Infection
title_full_unstemmed The BtaF Adhesin Is Necessary for Full Virulence During Respiratory Infection by Brucella suis and Is a Novel Immunogen for Nasal Vaccination Against Brucella Infection
title_sort The BtaF Adhesin Is Necessary for Full Virulence During Respiratory Infection by Brucella suis and Is a Novel Immunogen for Nasal Vaccination Against Brucella Infection
dc.creator.none.fl_str_mv Muñoz González, Florencia
Sycz, Gabriela
Alonso Paiva, Iván Mathias
Linke, Dirk
Zorreguieta, Ángeles
Baldi, Pablo Cesar
Ferrero, Mariana Cristina
author Muñoz González, Florencia
author_facet Muñoz González, Florencia
Sycz, Gabriela
Alonso Paiva, Iván Mathias
Linke, Dirk
Zorreguieta, Ángeles
Baldi, Pablo Cesar
Ferrero, Mariana Cristina
author_role author
author2 Sycz, Gabriela
Alonso Paiva, Iván Mathias
Linke, Dirk
Zorreguieta, Ángeles
Baldi, Pablo Cesar
Ferrero, Mariana Cristina
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv BACTERIAL ADHESINS
BRUCELLA SUIS
BTAF AUTOTRANSPORTER
INTRAGASTRIC CHALLENGE
MUCOSAL IMMUNITY
NASAL IMMUNIZATION
RESPIRATORY INFECTION
topic BACTERIAL ADHESINS
BRUCELLA SUIS
BTAF AUTOTRANSPORTER
INTRAGASTRIC CHALLENGE
MUCOSAL IMMUNITY
NASAL IMMUNIZATION
RESPIRATORY INFECTION
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Brucella enters their hosts mostly through mucosae from where it spreads systemically.Adhesion to extracellular matrix (ECM) components or to host cells is important for theinfectious process, and is mediated by several adhesins, including the BtaF trimericautotransporter. Although Th1 responses and gamma interferon (IFN-g) are important forprotection, antibodies able to block adhesions might also contribute to prevent Brucellainfection. We evaluated the importance of BtaF for respiratory Brucella infection, andcharacterized the immune response and protection from mucosal challenge induced bynasal vaccination with recombinant BtaF. While lung CFU numbers did not differ at day1 p.i. between mice intratracheally inoculated with B. suis M1330 (wild type) and thosereceiving a 1btaF mutant, they were reduced in the latter group at 7 and 30 days p.i.For vaccination studies the BtaF passenger domain was engineered and expressed asa soluble trimeric protein. Mice were immunized by the nasal route with BtaF or saline(control group) plus the mucosal adjuvant c-di-AMP. Specific anti-BtaF antibodies (IgGand IgA) were increased in serum, including a mixed IgG2a/IgG1 response. In vitro,these antibodies reduced bacterial adhesion to A549 alveolar epithelial cells. Specific IgAantibodies were also increased in several mucosae. Spleen cells from BtaF immunizedmice significantly increased their IL-2, IL-5, IL-17, and IFN-g secretion upon antigenstimulation. In cervical draining lymph nodes, antigen-experienced CD4+ T cells weremaintained mainly as central memory cells. A BtaF-specific delayed-type hypersensitivityresponse was detected in BtaF immunized mice. Lung cells from the latter producedhigh levels of IFN-g upon antigen stimulation. Although nasal immunization with BtaF didnot protect mice against B. suis respiratory challenge, it conferred significant protectionfrom intragastric challenge; the splenic load of B. suis was reduced by 3.28 log CFU inimmunized mice. This study shows that nasal vaccination with BtaF+c-di-AMP protectsagainst intragastric challenge with B. suis by inducing local and systemic antibodyresponses, central memory CD4+ T cells and strong Th1 responses. Therefore, althoughBtaF vaccination did not protect fromB. suis respiratory infection, this adhesin constitutesa promising immunogen against mucosal B. suis infection.
Fil: Muñoz González, Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; Argentina
Fil: Sycz, Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Fil: Alonso Paiva, Iván Mathias. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; Argentina
Fil: Linke, Dirk. Centro de Síntesis Ecológica y Evolutiva, Universidad de Oslo; Noruega
Fil: Zorreguieta, Ángeles. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Fil: Baldi, Pablo Cesar. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; Argentina
Fil: Ferrero, Mariana Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; Argentina
description Brucella enters their hosts mostly through mucosae from where it spreads systemically.Adhesion to extracellular matrix (ECM) components or to host cells is important for theinfectious process, and is mediated by several adhesins, including the BtaF trimericautotransporter. Although Th1 responses and gamma interferon (IFN-g) are important forprotection, antibodies able to block adhesions might also contribute to prevent Brucellainfection. We evaluated the importance of BtaF for respiratory Brucella infection, andcharacterized the immune response and protection from mucosal challenge induced bynasal vaccination with recombinant BtaF. While lung CFU numbers did not differ at day1 p.i. between mice intratracheally inoculated with B. suis M1330 (wild type) and thosereceiving a 1btaF mutant, they were reduced in the latter group at 7 and 30 days p.i.For vaccination studies the BtaF passenger domain was engineered and expressed asa soluble trimeric protein. Mice were immunized by the nasal route with BtaF or saline(control group) plus the mucosal adjuvant c-di-AMP. Specific anti-BtaF antibodies (IgGand IgA) were increased in serum, including a mixed IgG2a/IgG1 response. In vitro,these antibodies reduced bacterial adhesion to A549 alveolar epithelial cells. Specific IgAantibodies were also increased in several mucosae. Spleen cells from BtaF immunizedmice significantly increased their IL-2, IL-5, IL-17, and IFN-g secretion upon antigenstimulation. In cervical draining lymph nodes, antigen-experienced CD4+ T cells weremaintained mainly as central memory cells. A BtaF-specific delayed-type hypersensitivityresponse was detected in BtaF immunized mice. Lung cells from the latter producedhigh levels of IFN-g upon antigen stimulation. Although nasal immunization with BtaF didnot protect mice against B. suis respiratory challenge, it conferred significant protectionfrom intragastric challenge; the splenic load of B. suis was reduced by 3.28 log CFU inimmunized mice. This study shows that nasal vaccination with BtaF+c-di-AMP protectsagainst intragastric challenge with B. suis by inducing local and systemic antibodyresponses, central memory CD4+ T cells and strong Th1 responses. Therefore, althoughBtaF vaccination did not protect fromB. suis respiratory infection, this adhesin constitutesa promising immunogen against mucosal B. suis infection.
publishDate 2019
dc.date.none.fl_str_mv 2019-07-26
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/11336/121073
Muñoz González, Florencia; Sycz, Gabriela; Alonso Paiva, Iván Mathias; Linke, Dirk; Zorreguieta, Ángeles; et al.; The BtaF Adhesin Is Necessary for Full Virulence During Respiratory Infection by Brucella suis and Is a Novel Immunogen for Nasal Vaccination Against Brucella Infection; Frontiers Media S.A.; Frontiers in immunology; 10; 1775; 26-7-2019; 1-16
1664-3224
CONICET Digital
CONICET
url http://hdl.handle.net/11336/121073
identifier_str_mv Muñoz González, Florencia; Sycz, Gabriela; Alonso Paiva, Iván Mathias; Linke, Dirk; Zorreguieta, Ángeles; et al.; The BtaF Adhesin Is Necessary for Full Virulence During Respiratory Infection by Brucella suis and Is a Novel Immunogen for Nasal Vaccination Against Brucella Infection; Frontiers Media S.A.; Frontiers in immunology; 10; 1775; 26-7-2019; 1-16
1664-3224
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.frontiersin.org/article/10.3389/fimmu.2019.01775/full
info:eu-repo/semantics/altIdentifier/doi/10.3389/fimmu.2019.01775
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 Media S.A.
publisher.none.fl_str_mv Frontiers Media S.A.
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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