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

dc.creatorMalamud, Mariano
dc.creatorCarasi, Paula
dc.creatorAssandri, Matías Hernán
dc.creatorFreire, Teresa
dc.creatorLepenies, Bernd
dc.creatorSerradell, María de los Ángeles
dc.date2019
dc.date2020-10-23T12:34:46Z
dc.date.accessioned2023-07-14T22:44:59Z
dc.date.available2023-07-14T22:44:59Z
dc.identifierhttp://sedici.unlp.edu.ar/handle/10915/107592
dc.identifierhttp://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC6607945&blobtype=pdf
dc.identifierissn:1664-3224
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/7448061
dc.descriptionThe 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.
dc.descriptionInstituto de Estudios Inmunológicos y Fisiopatológicos
dc.formatapplication/pdf
dc.languageen
dc.rightshttp://creativecommons.org/licenses/by-nc-sa/4.0/
dc.rightsCreative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)
dc.subjectCiencias Exactas
dc.subjectS-layer protein
dc.subjectadjuvants
dc.subjectC-type lectin receptors
dc.subjectDCs activation
dc.subjectLactobacillus
dc.titleS-Layer Glycoprotein from <i>Lactobacillus kefiri</i> Exerts Its Immunostimulatory Activity Through Glycan Recognition by Mincle
dc.typeArticulo
dc.typeArticulo


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