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Mechanism of activation of porcine dendritic cells by an α-D-glucan nanoparticle adjuvant and a nanoparticle/poly(I:C) combination adjuvant

Recent studies have shown that corn-derived cationic α-D-glucan nanoparticles, known as Nano-11, significantly increase the immune response when used as a vaccine adjuvant in mice and in pigs. Furthermore, the nanoparticles can be formulated with other immunostimulators such as poly(I:C), which furt...

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Autores principales: Hernandez-Franco, Juan F., Xie, Shaojun, Thimmapuram, Jyothi, Ragland, Darryl, HogenEsch, Harm
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9483091/
https://www.ncbi.nlm.nih.gov/pubmed/36131928
http://dx.doi.org/10.3389/fimmu.2022.990900
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author Hernandez-Franco, Juan F.
Xie, Shaojun
Thimmapuram, Jyothi
Ragland, Darryl
HogenEsch, Harm
author_facet Hernandez-Franco, Juan F.
Xie, Shaojun
Thimmapuram, Jyothi
Ragland, Darryl
HogenEsch, Harm
author_sort Hernandez-Franco, Juan F.
collection PubMed
description Recent studies have shown that corn-derived cationic α-D-glucan nanoparticles, known as Nano-11, significantly increase the immune response when used as a vaccine adjuvant in mice and in pigs. Furthermore, the nanoparticles can be formulated with other immunostimulators such as poly(I:C), which further enhances the immune response. The current experiments were aimed at elucidating the mechanism of action of Nano-11 alone and in combination with poly(I:C). The effect of these adjuvants on porcine monocyte-derived dendritic cells (Mo-DCs) was determined by RNA-sequencing, supplemented with flow cytometry, cytokine analysis, and Western blots. Adsorption of poly(I:C) to Nano-11 reduced its cytotoxicity for Mo-DCs. Exposure of Mo-DCs to Nano-11 and Nano-11/poly(I:C) induced differential expression of 979 and 2016 genes, respectively. Gene Ontology enrichment and KEGG pathway analysis revealed many changes in gene expression related to inflammation, innate immunity, immune response to infections, and metabolism. Nano-11 and Nano-11/poly(I:C) induced maturation of the Mo-DCs as indicated by increased expression of costimulatory molecules and MHC II. Increased expression of genes downstream of p38 MAPK activation revealed a role for this signaling pathway in the activation of Mo-DCs by the adjuvants. This was confirmed by Western blot and inhibition of TNF-secretion upon incubation with the p38 inhibitor SB203580. These experiments provide insights into the mechanism of action of the novel adjuvants Nano-11 and Nano-11/poly(I:C).
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spelling pubmed-94830912022-09-20 Mechanism of activation of porcine dendritic cells by an α-D-glucan nanoparticle adjuvant and a nanoparticle/poly(I:C) combination adjuvant Hernandez-Franco, Juan F. Xie, Shaojun Thimmapuram, Jyothi Ragland, Darryl HogenEsch, Harm Front Immunol Immunology Recent studies have shown that corn-derived cationic α-D-glucan nanoparticles, known as Nano-11, significantly increase the immune response when used as a vaccine adjuvant in mice and in pigs. Furthermore, the nanoparticles can be formulated with other immunostimulators such as poly(I:C), which further enhances the immune response. The current experiments were aimed at elucidating the mechanism of action of Nano-11 alone and in combination with poly(I:C). The effect of these adjuvants on porcine monocyte-derived dendritic cells (Mo-DCs) was determined by RNA-sequencing, supplemented with flow cytometry, cytokine analysis, and Western blots. Adsorption of poly(I:C) to Nano-11 reduced its cytotoxicity for Mo-DCs. Exposure of Mo-DCs to Nano-11 and Nano-11/poly(I:C) induced differential expression of 979 and 2016 genes, respectively. Gene Ontology enrichment and KEGG pathway analysis revealed many changes in gene expression related to inflammation, innate immunity, immune response to infections, and metabolism. Nano-11 and Nano-11/poly(I:C) induced maturation of the Mo-DCs as indicated by increased expression of costimulatory molecules and MHC II. Increased expression of genes downstream of p38 MAPK activation revealed a role for this signaling pathway in the activation of Mo-DCs by the adjuvants. This was confirmed by Western blot and inhibition of TNF-secretion upon incubation with the p38 inhibitor SB203580. These experiments provide insights into the mechanism of action of the novel adjuvants Nano-11 and Nano-11/poly(I:C). Frontiers Media S.A. 2022-09-05 /pmc/articles/PMC9483091/ /pubmed/36131928 http://dx.doi.org/10.3389/fimmu.2022.990900 Text en Copyright © 2022 Hernandez-Franco, Xie, Thimmapuram, Ragland and HogenEsch https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Hernandez-Franco, Juan F.
Xie, Shaojun
Thimmapuram, Jyothi
Ragland, Darryl
HogenEsch, Harm
Mechanism of activation of porcine dendritic cells by an α-D-glucan nanoparticle adjuvant and a nanoparticle/poly(I:C) combination adjuvant
title Mechanism of activation of porcine dendritic cells by an α-D-glucan nanoparticle adjuvant and a nanoparticle/poly(I:C) combination adjuvant
title_full Mechanism of activation of porcine dendritic cells by an α-D-glucan nanoparticle adjuvant and a nanoparticle/poly(I:C) combination adjuvant
title_fullStr Mechanism of activation of porcine dendritic cells by an α-D-glucan nanoparticle adjuvant and a nanoparticle/poly(I:C) combination adjuvant
title_full_unstemmed Mechanism of activation of porcine dendritic cells by an α-D-glucan nanoparticle adjuvant and a nanoparticle/poly(I:C) combination adjuvant
title_short Mechanism of activation of porcine dendritic cells by an α-D-glucan nanoparticle adjuvant and a nanoparticle/poly(I:C) combination adjuvant
title_sort mechanism of activation of porcine dendritic cells by an α-d-glucan nanoparticle adjuvant and a nanoparticle/poly(i:c) combination adjuvant
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9483091/
https://www.ncbi.nlm.nih.gov/pubmed/36131928
http://dx.doi.org/10.3389/fimmu.2022.990900
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