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Metabolic Reprogramming of Macrophages upon In Vitro Incubation with Aluminum-Based Adjuvant

Aluminum-based adjuvants have been extensively used in vaccines. Despite their widespread use, the mechanism behind the immune stimulation properties of these adjuvants is not fully understood. Needless to say, extending the knowledge of the immune-stimulating properties of aluminum-based adjuvants...

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Autores principales: Danielsson, Ravi, Ferey, Nathan, Mile, Irene, Eriksson, Håkan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10002480/
https://www.ncbi.nlm.nih.gov/pubmed/36901849
http://dx.doi.org/10.3390/ijms24054409
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author Danielsson, Ravi
Ferey, Nathan
Mile, Irene
Eriksson, Håkan
author_facet Danielsson, Ravi
Ferey, Nathan
Mile, Irene
Eriksson, Håkan
author_sort Danielsson, Ravi
collection PubMed
description Aluminum-based adjuvants have been extensively used in vaccines. Despite their widespread use, the mechanism behind the immune stimulation properties of these adjuvants is not fully understood. Needless to say, extending the knowledge of the immune-stimulating properties of aluminum-based adjuvants is of utmost importance in the development of new, safer, and efficient vaccines. To further our knowledge of the mode of action of aluminum-based adjuvants, the prospect of metabolic reprogramming of macrophages upon phagocytosis of aluminum-based adjuvants was investigated. Macrophages were differentiated and polarized in vitro from human peripheral monocytes and incubated with the aluminum-based adjuvant Alhydrogel(®). Polarization was verified by the expression of CD markers and cytokine production. In order to recognize adjuvant-derived reprogramming, macrophages were incubated with Alhydrogel(®) or particles of polystyrene as control, and the cellular lactate content was analyzed using a bioluminescent assay. Quiescent M0 macrophages, as well as alternatively activated M2 macrophages, exhibited increased glycolytic metabolism upon exposure to aluminum-based adjuvants, indicating a metabolic reprogramming of the cells. Phagocytosis of aluminous adjuvants could result in an intracellular depot of aluminum ions, which may induce or support a metabolic reprogramming of the macrophages. The resulting increase in inflammatory macrophages could thus prove to be an important factor in the immune-stimulating properties of aluminum-based adjuvants.
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spelling pubmed-100024802023-03-11 Metabolic Reprogramming of Macrophages upon In Vitro Incubation with Aluminum-Based Adjuvant Danielsson, Ravi Ferey, Nathan Mile, Irene Eriksson, Håkan Int J Mol Sci Article Aluminum-based adjuvants have been extensively used in vaccines. Despite their widespread use, the mechanism behind the immune stimulation properties of these adjuvants is not fully understood. Needless to say, extending the knowledge of the immune-stimulating properties of aluminum-based adjuvants is of utmost importance in the development of new, safer, and efficient vaccines. To further our knowledge of the mode of action of aluminum-based adjuvants, the prospect of metabolic reprogramming of macrophages upon phagocytosis of aluminum-based adjuvants was investigated. Macrophages were differentiated and polarized in vitro from human peripheral monocytes and incubated with the aluminum-based adjuvant Alhydrogel(®). Polarization was verified by the expression of CD markers and cytokine production. In order to recognize adjuvant-derived reprogramming, macrophages were incubated with Alhydrogel(®) or particles of polystyrene as control, and the cellular lactate content was analyzed using a bioluminescent assay. Quiescent M0 macrophages, as well as alternatively activated M2 macrophages, exhibited increased glycolytic metabolism upon exposure to aluminum-based adjuvants, indicating a metabolic reprogramming of the cells. Phagocytosis of aluminous adjuvants could result in an intracellular depot of aluminum ions, which may induce or support a metabolic reprogramming of the macrophages. The resulting increase in inflammatory macrophages could thus prove to be an important factor in the immune-stimulating properties of aluminum-based adjuvants. MDPI 2023-02-23 /pmc/articles/PMC10002480/ /pubmed/36901849 http://dx.doi.org/10.3390/ijms24054409 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Danielsson, Ravi
Ferey, Nathan
Mile, Irene
Eriksson, Håkan
Metabolic Reprogramming of Macrophages upon In Vitro Incubation with Aluminum-Based Adjuvant
title Metabolic Reprogramming of Macrophages upon In Vitro Incubation with Aluminum-Based Adjuvant
title_full Metabolic Reprogramming of Macrophages upon In Vitro Incubation with Aluminum-Based Adjuvant
title_fullStr Metabolic Reprogramming of Macrophages upon In Vitro Incubation with Aluminum-Based Adjuvant
title_full_unstemmed Metabolic Reprogramming of Macrophages upon In Vitro Incubation with Aluminum-Based Adjuvant
title_short Metabolic Reprogramming of Macrophages upon In Vitro Incubation with Aluminum-Based Adjuvant
title_sort metabolic reprogramming of macrophages upon in vitro incubation with aluminum-based adjuvant
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10002480/
https://www.ncbi.nlm.nih.gov/pubmed/36901849
http://dx.doi.org/10.3390/ijms24054409
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