Cargando…

Vitamin D Treatment Sequence Is Critical for Transcriptome Modulation of Immune Challenged Primary Human Cells

Microbe-associated molecular patterns, such as lipopolysaccharide (LPS) and β-glucan (BG), are surrogates of immune challenges like bacterial and fungal infections, respectively. The biologically active form of vitamin D, 1α,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)), supports the immune system in i...

Descripción completa

Detalles Bibliográficos
Autores principales: Malmberg, Henna-Riikka, Hanel, Andrea, Taipale, Mari, Heikkinen, Sami, Carlberg, Carsten
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8702862/
https://www.ncbi.nlm.nih.gov/pubmed/34956186
http://dx.doi.org/10.3389/fimmu.2021.754056
_version_ 1784621335304994816
author Malmberg, Henna-Riikka
Hanel, Andrea
Taipale, Mari
Heikkinen, Sami
Carlberg, Carsten
author_facet Malmberg, Henna-Riikka
Hanel, Andrea
Taipale, Mari
Heikkinen, Sami
Carlberg, Carsten
author_sort Malmberg, Henna-Riikka
collection PubMed
description Microbe-associated molecular patterns, such as lipopolysaccharide (LPS) and β-glucan (BG), are surrogates of immune challenges like bacterial and fungal infections, respectively. The biologically active form of vitamin D, 1α,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)), supports the immune system in its fight against infections. This study investigated significant and prominent changes of the transcriptome of human peripheral blood mononuclear cells that immediately after isolation are exposed to 1,25(OH)(2)D(3)-modulated immune challenges over a time frame of 24-48 h. In this in vitro study design, most LPS and BG responsive genes are downregulated and their counts are drastically reduced when cells are treated 24 h after, 24 h before or in parallel with 1,25(OH)(2)D(3). Interestingly, only a 1,25(OH)(2)D(3) pre-treatment of the LPS challenge results in a majority of upregulated genes. Based on transcriptome-wide data both immune challenges display characteristic differences in responsive genes and their associated pathways, to which the actions of 1,25(OH)(2)D(3) often oppose. The joined BG/1,25(OH)(2)D(3) response is less sensitive to treatment sequence than that of LPS/1,25(OH)(2)D(3). In conclusion, the functional consequences of immune challenges are significantly modulated by 1,25(OH)(2)D(3) but largely depend on treatment sequence. This may suggest that a sufficient vitamin D status before an infection is more important than vitamin D supplementation afterwards.
format Online
Article
Text
id pubmed-8702862
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-87028622021-12-25 Vitamin D Treatment Sequence Is Critical for Transcriptome Modulation of Immune Challenged Primary Human Cells Malmberg, Henna-Riikka Hanel, Andrea Taipale, Mari Heikkinen, Sami Carlberg, Carsten Front Immunol Immunology Microbe-associated molecular patterns, such as lipopolysaccharide (LPS) and β-glucan (BG), are surrogates of immune challenges like bacterial and fungal infections, respectively. The biologically active form of vitamin D, 1α,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)), supports the immune system in its fight against infections. This study investigated significant and prominent changes of the transcriptome of human peripheral blood mononuclear cells that immediately after isolation are exposed to 1,25(OH)(2)D(3)-modulated immune challenges over a time frame of 24-48 h. In this in vitro study design, most LPS and BG responsive genes are downregulated and their counts are drastically reduced when cells are treated 24 h after, 24 h before or in parallel with 1,25(OH)(2)D(3). Interestingly, only a 1,25(OH)(2)D(3) pre-treatment of the LPS challenge results in a majority of upregulated genes. Based on transcriptome-wide data both immune challenges display characteristic differences in responsive genes and their associated pathways, to which the actions of 1,25(OH)(2)D(3) often oppose. The joined BG/1,25(OH)(2)D(3) response is less sensitive to treatment sequence than that of LPS/1,25(OH)(2)D(3). In conclusion, the functional consequences of immune challenges are significantly modulated by 1,25(OH)(2)D(3) but largely depend on treatment sequence. This may suggest that a sufficient vitamin D status before an infection is more important than vitamin D supplementation afterwards. Frontiers Media S.A. 2021-12-10 /pmc/articles/PMC8702862/ /pubmed/34956186 http://dx.doi.org/10.3389/fimmu.2021.754056 Text en Copyright © 2021 Malmberg, Hanel, Taipale, Heikkinen and Carlberg 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
Malmberg, Henna-Riikka
Hanel, Andrea
Taipale, Mari
Heikkinen, Sami
Carlberg, Carsten
Vitamin D Treatment Sequence Is Critical for Transcriptome Modulation of Immune Challenged Primary Human Cells
title Vitamin D Treatment Sequence Is Critical for Transcriptome Modulation of Immune Challenged Primary Human Cells
title_full Vitamin D Treatment Sequence Is Critical for Transcriptome Modulation of Immune Challenged Primary Human Cells
title_fullStr Vitamin D Treatment Sequence Is Critical for Transcriptome Modulation of Immune Challenged Primary Human Cells
title_full_unstemmed Vitamin D Treatment Sequence Is Critical for Transcriptome Modulation of Immune Challenged Primary Human Cells
title_short Vitamin D Treatment Sequence Is Critical for Transcriptome Modulation of Immune Challenged Primary Human Cells
title_sort vitamin d treatment sequence is critical for transcriptome modulation of immune challenged primary human cells
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8702862/
https://www.ncbi.nlm.nih.gov/pubmed/34956186
http://dx.doi.org/10.3389/fimmu.2021.754056
work_keys_str_mv AT malmberghennariikka vitamindtreatmentsequenceiscriticalfortranscriptomemodulationofimmunechallengedprimaryhumancells
AT hanelandrea vitamindtreatmentsequenceiscriticalfortranscriptomemodulationofimmunechallengedprimaryhumancells
AT taipalemari vitamindtreatmentsequenceiscriticalfortranscriptomemodulationofimmunechallengedprimaryhumancells
AT heikkinensami vitamindtreatmentsequenceiscriticalfortranscriptomemodulationofimmunechallengedprimaryhumancells
AT carlbergcarsten vitamindtreatmentsequenceiscriticalfortranscriptomemodulationofimmunechallengedprimaryhumancells