S-Layer glycoprotein from Lactobacillus kefiri exerts its immunostimulatory activity through glycan recognition by Mincle

Autores
Malamud, Mariano; Carasi, Paula; Assandri, Matías Hernán; Freire, Teresa; Lepenies, Bernd; Serradell, María de los Ángeles
Año de publicación
2019
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The development of new subunit vaccines has promoted the rational design of adjuvants able to induce a strong T-cell activation by targeting specific immune receptors. The S-layer is a (glyco)-proteinaceous envelope constituted by subunits that self-assemble to form a two-dimensional lattice that covers the surface of different species of Bacteria and Archaea. Due to their ability to self-assemble in solution, they are attractive tools to be used as antigen/hapten carriers or adjuvants. Recently, we have demonstrated that S-layer glycoprotein from Lactobacillus kefiri CIDCA 8348 (SLP-8348) enhanced the LPS-induced response on macrophages in a Ca2+-dependent manner, but the receptors involved in these immunomodulatory properties remain unknown. Therefore, we aim to determine the C-type lectin receptors (CLRs) recognizing this bacterial surface glycoprotein as well as to investigate the role of glycans in both the immunogenicity and adjuvant capacity of SLP-8348. Here, using a mild periodate oxidation protocol, we showed that loss of SLP-8348 glycan integrity impairs the cell-mediated immune response against the protein. Moreover, our data indicate that the adjuvant capacity of SLP-8348 is also dependent of the biological activity of the SLP-8348 glycans. In order to evaluate the CLRs involved in the interaction with SLP-8348 an ELISA-based method using CLR–hFc fusion proteins showed that SLP-8348 interacts with different CLRs such as Mincle, SingR3, and hDC-SIGN. Using BMDCs derived from CLR-deficient mice, we show that SLP-8348 uptake is dependent of Mincle. Furthermore, we demonstrate that the SLP-8348-induced activation of BMDCs as well as its adjuvant capacity relies on the presence of Mincle and its signaling adaptor CARD9 on BMDCs, since SLP-8348-activated BMDCs from Mincle−/− or CARD9−/− mice were not capable to enhance OVA-specific response in CD4+ T cells purified from OT-II mice. These findings significantly contribute to the understanding of the role of glycans in the immunomodulation elicited by bacterial SLPs and generate a great opportunity in the search for new adjuvants derived from non-pathogenic microorganisms.
Fil: Malamud, Mariano. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Cátedra de Microbiología General; Argentina. University of Veterinary Medicine Hannover; Alemania. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina
Fil: Carasi, Paula. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Cátedra de Microbiología General; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Estudios Inmunológicos y Fisiopatológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Estudios Inmunológicos y Fisiopatológicos; Argentina
Fil: Assandri, Matías Hernán. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Cátedra de Microbiología General; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina
Fil: Freire, Teresa. Universidad de la República; Uruguay
Fil: Lepenies, Bernd. University of Veterinary Medicine Hannover; Alemania
Fil: Serradell, María de los Ángeles. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Cátedra de Microbiología General; Argentina. Universidad Nacional Arturo Jauretche; Argentina
Materia
S-LAYER PROTEIN
ADJUVANTS
C-TYPE LECTIN RECEPTORS
LACTOBACILLUS
DCs ACTIVATION
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/152228
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/152228
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling S-Layer glycoprotein from Lactobacillus kefiri exerts its immunostimulatory activity through glycan recognition by MincleMalamud, MarianoCarasi, PaulaAssandri, Matías HernánFreire, TeresaLepenies, BerndSerradell, María de los ÁngelesS-LAYER PROTEINADJUVANTSC-TYPE LECTIN RECEPTORSLACTOBACILLUSDCs ACTIVATIONhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1The development of new subunit vaccines has promoted the rational design of adjuvants able to induce a strong T-cell activation by targeting specific immune receptors. The S-layer is a (glyco)-proteinaceous envelope constituted by subunits that self-assemble to form a two-dimensional lattice that covers the surface of different species of Bacteria and Archaea. Due to their ability to self-assemble in solution, they are attractive tools to be used as antigen/hapten carriers or adjuvants. Recently, we have demonstrated that S-layer glycoprotein from Lactobacillus kefiri CIDCA 8348 (SLP-8348) enhanced the LPS-induced response on macrophages in a Ca2+-dependent manner, but the receptors involved in these immunomodulatory properties remain unknown. Therefore, we aim to determine the C-type lectin receptors (CLRs) recognizing this bacterial surface glycoprotein as well as to investigate the role of glycans in both the immunogenicity and adjuvant capacity of SLP-8348. Here, using a mild periodate oxidation protocol, we showed that loss of SLP-8348 glycan integrity impairs the cell-mediated immune response against the protein. Moreover, our data indicate that the adjuvant capacity of SLP-8348 is also dependent of the biological activity of the SLP-8348 glycans. In order to evaluate the CLRs involved in the interaction with SLP-8348 an ELISA-based method using CLR–hFc fusion proteins showed that SLP-8348 interacts with different CLRs such as Mincle, SingR3, and hDC-SIGN. Using BMDCs derived from CLR-deficient mice, we show that SLP-8348 uptake is dependent of Mincle. Furthermore, we demonstrate that the SLP-8348-induced activation of BMDCs as well as its adjuvant capacity relies on the presence of Mincle and its signaling adaptor CARD9 on BMDCs, since SLP-8348-activated BMDCs from Mincle−/− or CARD9−/− mice were not capable to enhance OVA-specific response in CD4+ T cells purified from OT-II mice. These findings significantly contribute to the understanding of the role of glycans in the immunomodulation elicited by bacterial SLPs and generate a great opportunity in the search for new adjuvants derived from non-pathogenic microorganisms.Fil: Malamud, Mariano. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Cátedra de Microbiología General; Argentina. University of Veterinary Medicine Hannover; Alemania. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; ArgentinaFil: Carasi, Paula. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Cátedra de Microbiología General; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Estudios Inmunológicos y Fisiopatológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Estudios Inmunológicos y Fisiopatológicos; ArgentinaFil: Assandri, Matías Hernán. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Cátedra de Microbiología General; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; ArgentinaFil: Freire, Teresa. Universidad de la República; UruguayFil: Lepenies, Bernd. University of Veterinary Medicine Hannover; AlemaniaFil: Serradell, María de los Ángeles. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Cátedra de Microbiología General; Argentina. Universidad Nacional Arturo Jauretche; ArgentinaFrontiers Media2019-06-26info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/152228Malamud, Mariano; Carasi, Paula; Assandri, Matías Hernán; Freire, Teresa; Lepenies, Bernd; et al.; S-Layer glycoprotein from Lactobacillus kefiri exerts its immunostimulatory activity through glycan recognition by Mincle; Frontiers Media; Frontiers in Immunology; 10; 26-6-2019; 1-111664-3224CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.3389/fimmu.2019.01422info:eu-repo/semantics/altIdentifier/url/https://www.frontiersin.org/articles/10.3389/fimmu.2019.01422/fullinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:59:46Zoai:ri.conicet.gov.ar:11336/152228instacron: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 09:59:46.909CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv S-Layer glycoprotein from Lactobacillus kefiri exerts its immunostimulatory activity through glycan recognition by Mincle
title S-Layer glycoprotein from Lactobacillus kefiri exerts its immunostimulatory activity through glycan recognition by Mincle
spellingShingle S-Layer glycoprotein from Lactobacillus kefiri exerts its immunostimulatory activity through glycan recognition by Mincle
Malamud, Mariano
S-LAYER PROTEIN
ADJUVANTS
C-TYPE LECTIN RECEPTORS
LACTOBACILLUS
DCs ACTIVATION
title_short S-Layer glycoprotein from Lactobacillus kefiri exerts its immunostimulatory activity through glycan recognition by Mincle
title_full S-Layer glycoprotein from Lactobacillus kefiri exerts its immunostimulatory activity through glycan recognition by Mincle
title_fullStr S-Layer glycoprotein from Lactobacillus kefiri exerts its immunostimulatory activity through glycan recognition by Mincle
title_full_unstemmed S-Layer glycoprotein from Lactobacillus kefiri exerts its immunostimulatory activity through glycan recognition by Mincle
title_sort S-Layer glycoprotein from Lactobacillus kefiri exerts its immunostimulatory activity through glycan recognition by Mincle
dc.creator.none.fl_str_mv Malamud, Mariano
Carasi, Paula
Assandri, Matías Hernán
Freire, Teresa
Lepenies, Bernd
Serradell, María de los Ángeles
author Malamud, Mariano
author_facet Malamud, Mariano
Carasi, Paula
Assandri, Matías Hernán
Freire, Teresa
Lepenies, Bernd
Serradell, María de los Ángeles
author_role author
author2 Carasi, Paula
Assandri, Matías Hernán
Freire, Teresa
Lepenies, Bernd
Serradell, María de los Ángeles
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv S-LAYER PROTEIN
ADJUVANTS
C-TYPE LECTIN RECEPTORS
LACTOBACILLUS
DCs ACTIVATION
topic S-LAYER PROTEIN
ADJUVANTS
C-TYPE LECTIN RECEPTORS
LACTOBACILLUS
DCs ACTIVATION
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv The development of new subunit vaccines has promoted the rational design of adjuvants able to induce a strong T-cell activation by targeting specific immune receptors. The S-layer is a (glyco)-proteinaceous envelope constituted by subunits that self-assemble to form a two-dimensional lattice that covers the surface of different species of Bacteria and Archaea. Due to their ability to self-assemble in solution, they are attractive tools to be used as antigen/hapten carriers or adjuvants. Recently, we have demonstrated that S-layer glycoprotein from Lactobacillus kefiri CIDCA 8348 (SLP-8348) enhanced the LPS-induced response on macrophages in a Ca2+-dependent manner, but the receptors involved in these immunomodulatory properties remain unknown. Therefore, we aim to determine the C-type lectin receptors (CLRs) recognizing this bacterial surface glycoprotein as well as to investigate the role of glycans in both the immunogenicity and adjuvant capacity of SLP-8348. Here, using a mild periodate oxidation protocol, we showed that loss of SLP-8348 glycan integrity impairs the cell-mediated immune response against the protein. Moreover, our data indicate that the adjuvant capacity of SLP-8348 is also dependent of the biological activity of the SLP-8348 glycans. In order to evaluate the CLRs involved in the interaction with SLP-8348 an ELISA-based method using CLR–hFc fusion proteins showed that SLP-8348 interacts with different CLRs such as Mincle, SingR3, and hDC-SIGN. Using BMDCs derived from CLR-deficient mice, we show that SLP-8348 uptake is dependent of Mincle. Furthermore, we demonstrate that the SLP-8348-induced activation of BMDCs as well as its adjuvant capacity relies on the presence of Mincle and its signaling adaptor CARD9 on BMDCs, since SLP-8348-activated BMDCs from Mincle−/− or CARD9−/− mice were not capable to enhance OVA-specific response in CD4+ T cells purified from OT-II mice. These findings significantly contribute to the understanding of the role of glycans in the immunomodulation elicited by bacterial SLPs and generate a great opportunity in the search for new adjuvants derived from non-pathogenic microorganisms.
Fil: Malamud, Mariano. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Cátedra de Microbiología General; Argentina. University of Veterinary Medicine Hannover; Alemania. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina
Fil: Carasi, Paula. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Cátedra de Microbiología General; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Estudios Inmunológicos y Fisiopatológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Estudios Inmunológicos y Fisiopatológicos; Argentina
Fil: Assandri, Matías Hernán. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Cátedra de Microbiología General; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina
Fil: Freire, Teresa. Universidad de la República; Uruguay
Fil: Lepenies, Bernd. University of Veterinary Medicine Hannover; Alemania
Fil: Serradell, María de los Ángeles. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Cátedra de Microbiología General; Argentina. Universidad Nacional Arturo Jauretche; Argentina
description The development of new subunit vaccines has promoted the rational design of adjuvants able to induce a strong T-cell activation by targeting specific immune receptors. The S-layer is a (glyco)-proteinaceous envelope constituted by subunits that self-assemble to form a two-dimensional lattice that covers the surface of different species of Bacteria and Archaea. Due to their ability to self-assemble in solution, they are attractive tools to be used as antigen/hapten carriers or adjuvants. Recently, we have demonstrated that S-layer glycoprotein from Lactobacillus kefiri CIDCA 8348 (SLP-8348) enhanced the LPS-induced response on macrophages in a Ca2+-dependent manner, but the receptors involved in these immunomodulatory properties remain unknown. Therefore, we aim to determine the C-type lectin receptors (CLRs) recognizing this bacterial surface glycoprotein as well as to investigate the role of glycans in both the immunogenicity and adjuvant capacity of SLP-8348. Here, using a mild periodate oxidation protocol, we showed that loss of SLP-8348 glycan integrity impairs the cell-mediated immune response against the protein. Moreover, our data indicate that the adjuvant capacity of SLP-8348 is also dependent of the biological activity of the SLP-8348 glycans. In order to evaluate the CLRs involved in the interaction with SLP-8348 an ELISA-based method using CLR–hFc fusion proteins showed that SLP-8348 interacts with different CLRs such as Mincle, SingR3, and hDC-SIGN. Using BMDCs derived from CLR-deficient mice, we show that SLP-8348 uptake is dependent of Mincle. Furthermore, we demonstrate that the SLP-8348-induced activation of BMDCs as well as its adjuvant capacity relies on the presence of Mincle and its signaling adaptor CARD9 on BMDCs, since SLP-8348-activated BMDCs from Mincle−/− or CARD9−/− mice were not capable to enhance OVA-specific response in CD4+ T cells purified from OT-II mice. These findings significantly contribute to the understanding of the role of glycans in the immunomodulation elicited by bacterial SLPs and generate a great opportunity in the search for new adjuvants derived from non-pathogenic microorganisms.
publishDate 2019
dc.date.none.fl_str_mv 2019-06-26
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/11336/152228
Malamud, Mariano; Carasi, Paula; Assandri, Matías Hernán; Freire, Teresa; Lepenies, Bernd; et al.; S-Layer glycoprotein from Lactobacillus kefiri exerts its immunostimulatory activity through glycan recognition by Mincle; Frontiers Media; Frontiers in Immunology; 10; 26-6-2019; 1-11
1664-3224
CONICET Digital
CONICET
url http://hdl.handle.net/11336/152228
identifier_str_mv Malamud, Mariano; Carasi, Paula; Assandri, Matías Hernán; Freire, Teresa; Lepenies, Bernd; et al.; S-Layer glycoprotein from Lactobacillus kefiri exerts its immunostimulatory activity through glycan recognition by Mincle; Frontiers Media; Frontiers in Immunology; 10; 26-6-2019; 1-11
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/doi/10.3389/fimmu.2019.01422
info:eu-repo/semantics/altIdentifier/url/https://www.frontiersin.org/articles/10.3389/fimmu.2019.01422/full
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Frontiers Media
publisher.none.fl_str_mv Frontiers Media
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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