S-Layer Glycoprotein from <i>Lactobacillus kefiri</i> Exerts Its Immunostimulatory Activity Through Glycan Recognition by Mincle

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 co...

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Detalles Bibliográficos
Autores principales: Malamud, Mariano, Carasi, Paula, Assandri, Matías Hernán, Freire, Teresa, Lepenies, Bernd, Serradell, María de los Ángeles
Formato: Articulo
Lenguaje:Inglés
Publicado: 2019
Materias:
Ciencias Exactas
S-layer protein
adjuvants
C-type lectin receptors
DCs activation
Lactobacillus
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/107592
http://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC6607945&blobtype=pdf
Aporte de:
SEDICI (UNLP) de Universidad Nacional de La Plata
id I19-R120-10915-107592
record_format dspace
institution Universidad Nacional de La Plata
institution_str I-19
repository_str R-120
collection SEDICI (UNLP)
language Inglés
topic Ciencias Exactas
S-layer protein
adjuvants
C-type lectin receptors
DCs activation
Lactobacillus
spellingShingle Ciencias Exactas
S-layer protein
adjuvants
C-type lectin receptors
DCs activation
Lactobacillus
Malamud, Mariano
Carasi, Paula
Assandri, Matías Hernán
Freire, Teresa
Lepenies, Bernd
Serradell, María de los Ángeles
S-Layer Glycoprotein from <i>Lactobacillus kefiri</i> Exerts Its Immunostimulatory Activity Through Glycan Recognition by Mincle
topic_facet Ciencias Exactas
S-layer protein
adjuvants
C-type lectin receptors
DCs activation
Lactobacillus
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.
format Articulo
Articulo
author Malamud, Mariano
Carasi, Paula
Assandri, Matías Hernán
Freire, Teresa
Lepenies, Bernd
Serradell, María de los Ángeles
author_facet Malamud, Mariano
Carasi, Paula
Assandri, Matías Hernán
Freire, Teresa
Lepenies, Bernd
Serradell, María de los Ángeles
author_sort Malamud, Mariano
title S-Layer Glycoprotein from <i>Lactobacillus kefiri</i> Exerts Its Immunostimulatory Activity Through Glycan Recognition by Mincle
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
publishDate 2019
url http://sedici.unlp.edu.ar/handle/10915/107592
http://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC6607945&blobtype=pdf
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