S-Layer Glycoprotein from <i>Lactobacillus kefiri</i> 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.
Instituto de Estudios Inmunológicos y Fisiopatológicos - Materia
-
Ciencias Exactas
S-layer protein
adjuvants
C-type lectin receptors
DCs activation
Lactobacillus - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- http://creativecommons.org/licenses/by-nc-sa/4.0/
- Repositorio
- Institución
- Universidad Nacional de La Plata
- OAI Identificador
- oai:sedici.unlp.edu.ar:10915/107592
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S-Layer Glycoprotein from <i>Lactobacillus kefiri</i> Exerts Its Immunostimulatory Activity Through Glycan Recognition by MincleMalamud, MarianoCarasi, PaulaAssandri, Matías HernánFreire, TeresaLepenies, BerndSerradell, María de los ÁngelesCiencias ExactasS-layer proteinadjuvantsC-type lectin receptorsDCs activationLactobacillusThe 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.Instituto de Estudios Inmunológicos y Fisiopatológicos2019info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionArticulohttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfhttp://sedici.unlp.edu.ar/handle/10915/107592enginfo:eu-repo/semantics/altIdentifier/url/http://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC6607945&blobtype=pdfinfo:eu-repo/semantics/altIdentifier/issn/1664-3224info:eu-repo/semantics/altIdentifier/pmid/31297112info:eu-repo/semantics/altIdentifier/doi/10.3389/fimmu.2019.01422info:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by-nc-sa/4.0/Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)reponame:SEDICI (UNLP)instname:Universidad Nacional de La Platainstacron:UNLP2025-09-29T11:23:52Zoai:sedici.unlp.edu.ar:10915/107592Institucionalhttp://sedici.unlp.edu.ar/Universidad públicaNo correspondehttp://sedici.unlp.edu.ar/oai/snrdalira@sedici.unlp.edu.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:13292025-09-29 11:23:52.882SEDICI (UNLP) - Universidad Nacional de La Platafalse |
dc.title.none.fl_str_mv |
S-Layer Glycoprotein from <i>Lactobacillus kefiri</i> Exerts Its Immunostimulatory Activity Through Glycan Recognition by Mincle |
title |
S-Layer Glycoprotein from <i>Lactobacillus kefiri</i> Exerts Its Immunostimulatory Activity Through Glycan Recognition by Mincle |
spellingShingle |
S-Layer Glycoprotein from <i>Lactobacillus kefiri</i> Exerts Its Immunostimulatory Activity Through Glycan Recognition by Mincle Malamud, Mariano Ciencias Exactas S-layer protein adjuvants C-type lectin receptors DCs activation Lactobacillus |
title_short |
S-Layer Glycoprotein from <i>Lactobacillus kefiri</i> Exerts Its Immunostimulatory Activity Through Glycan Recognition by Mincle |
title_full |
S-Layer Glycoprotein from <i>Lactobacillus kefiri</i> Exerts Its Immunostimulatory Activity Through Glycan Recognition by Mincle |
title_fullStr |
S-Layer Glycoprotein from <i>Lactobacillus kefiri</i> Exerts Its Immunostimulatory Activity Through Glycan Recognition by Mincle |
title_full_unstemmed |
S-Layer Glycoprotein from <i>Lactobacillus kefiri</i> Exerts Its Immunostimulatory Activity Through Glycan Recognition by Mincle |
title_sort |
S-Layer Glycoprotein from <i>Lactobacillus kefiri</i> 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 |
Ciencias Exactas S-layer protein adjuvants C-type lectin receptors DCs activation Lactobacillus |
topic |
Ciencias Exactas S-layer protein adjuvants C-type lectin receptors DCs activation Lactobacillus |
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. Instituto de Estudios Inmunológicos y Fisiopatológicos |
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 |
dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Articulo http://purl.org/coar/resource_type/c_6501 info:ar-repo/semantics/articulo |
format |
article |
status_str |
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eng |
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eng |
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http://creativecommons.org/licenses/by-nc-sa/4.0/ Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) |
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