Cargando…
Fecal microbiota composition associates with the capacity of human peripheral blood monocytes to differentiate into immunogenic dendritic cells in vitro
Although promising for active immunization in cancer patients, dendritic cells (DCs) vaccines generated in vitro display high inter-individual variability in their immunogenicity, which mostly limits their therapeutic efficacy. Gut microbiota composition is a key emerging factor affecting individual...
Autores principales: | , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Taylor & Francis
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8115579/ https://www.ncbi.nlm.nih.gov/pubmed/33970783 http://dx.doi.org/10.1080/19490976.2021.1921927 |
_version_ | 1783691229746167808 |
---|---|
author | Radojević, Dušan Tomić, Sergej Mihajlović, Dušan Tolinački, Maja Pavlović, Bojan Vučević, Dragana Bojić, Svetlana Golić, Nataša Čolić, Miodrag Đokić, Jelena |
author_facet | Radojević, Dušan Tomić, Sergej Mihajlović, Dušan Tolinački, Maja Pavlović, Bojan Vučević, Dragana Bojić, Svetlana Golić, Nataša Čolić, Miodrag Đokić, Jelena |
author_sort | Radojević, Dušan |
collection | PubMed |
description | Although promising for active immunization in cancer patients, dendritic cells (DCs) vaccines generated in vitro display high inter-individual variability in their immunogenicity, which mostly limits their therapeutic efficacy. Gut microbiota composition is a key emerging factor affecting individuals’ immune responses, but it is unknown how it affects the variability of donors’ precursor cells to differentiate into immunogenic DCs in vitro. By analyzing gut microbiota composition in 14 healthy donors, along with the phenotype and cytokines production by monocyte-derived DCs, we found significant correlations between immunogenic properties of DC and microbiota composition. Namely, donors who had higher α-diversity of gut microbiota and higher abundance of short-chain fatty acid (SCFAs) and SCFA-producing bacteria in feces, displayed lower expression of CD1a on immature (im)DC and higher expression of ILT-3, costimulatory molecules (CD86, CD40) proinflammatory cytokines (TNF-α, IL-6, IL-8) and IL-12p70/IL-10 ratio, all of which correlated with their lower maturation potential and immunogenicity upon stimulation with LPS/IFNγ, a well-known Th1 polarizing cocktail. In contrast, imDCs generated from donors with lower α-diversity and higher abundance of Bifidobacterium and Collinsella in feces displayed higher CD1a expression and higher potential to up-regulate CD86 and CD40, increase TNF-α, IL-6, IL-8 production, and IL-12p70/IL-10 ratio upon stimulation. These results emphasize the important role of gut microbiota on the capacity of donor precursor cells to differentiate into immunogenic DCs suitable for cancer therapy, which could be harnessed for improving the actual and future DC-based cancer therapies. |
format | Online Article Text |
id | pubmed-8115579 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Taylor & Francis |
record_format | MEDLINE/PubMed |
spelling | pubmed-81155792021-05-21 Fecal microbiota composition associates with the capacity of human peripheral blood monocytes to differentiate into immunogenic dendritic cells in vitro Radojević, Dušan Tomić, Sergej Mihajlović, Dušan Tolinački, Maja Pavlović, Bojan Vučević, Dragana Bojić, Svetlana Golić, Nataša Čolić, Miodrag Đokić, Jelena Gut Microbes Research Paper Although promising for active immunization in cancer patients, dendritic cells (DCs) vaccines generated in vitro display high inter-individual variability in their immunogenicity, which mostly limits their therapeutic efficacy. Gut microbiota composition is a key emerging factor affecting individuals’ immune responses, but it is unknown how it affects the variability of donors’ precursor cells to differentiate into immunogenic DCs in vitro. By analyzing gut microbiota composition in 14 healthy donors, along with the phenotype and cytokines production by monocyte-derived DCs, we found significant correlations between immunogenic properties of DC and microbiota composition. Namely, donors who had higher α-diversity of gut microbiota and higher abundance of short-chain fatty acid (SCFAs) and SCFA-producing bacteria in feces, displayed lower expression of CD1a on immature (im)DC and higher expression of ILT-3, costimulatory molecules (CD86, CD40) proinflammatory cytokines (TNF-α, IL-6, IL-8) and IL-12p70/IL-10 ratio, all of which correlated with their lower maturation potential and immunogenicity upon stimulation with LPS/IFNγ, a well-known Th1 polarizing cocktail. In contrast, imDCs generated from donors with lower α-diversity and higher abundance of Bifidobacterium and Collinsella in feces displayed higher CD1a expression and higher potential to up-regulate CD86 and CD40, increase TNF-α, IL-6, IL-8 production, and IL-12p70/IL-10 ratio upon stimulation. These results emphasize the important role of gut microbiota on the capacity of donor precursor cells to differentiate into immunogenic DCs suitable for cancer therapy, which could be harnessed for improving the actual and future DC-based cancer therapies. Taylor & Francis 2021-05-10 /pmc/articles/PMC8115579/ /pubmed/33970783 http://dx.doi.org/10.1080/19490976.2021.1921927 Text en © 2021 The Author(s). Published with license by Taylor & Francis Group, LLC. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Paper Radojević, Dušan Tomić, Sergej Mihajlović, Dušan Tolinački, Maja Pavlović, Bojan Vučević, Dragana Bojić, Svetlana Golić, Nataša Čolić, Miodrag Đokić, Jelena Fecal microbiota composition associates with the capacity of human peripheral blood monocytes to differentiate into immunogenic dendritic cells in vitro |
title | Fecal microbiota composition associates with the capacity of human peripheral blood monocytes to differentiate into immunogenic dendritic cells in vitro |
title_full | Fecal microbiota composition associates with the capacity of human peripheral blood monocytes to differentiate into immunogenic dendritic cells in vitro |
title_fullStr | Fecal microbiota composition associates with the capacity of human peripheral blood monocytes to differentiate into immunogenic dendritic cells in vitro |
title_full_unstemmed | Fecal microbiota composition associates with the capacity of human peripheral blood monocytes to differentiate into immunogenic dendritic cells in vitro |
title_short | Fecal microbiota composition associates with the capacity of human peripheral blood monocytes to differentiate into immunogenic dendritic cells in vitro |
title_sort | fecal microbiota composition associates with the capacity of human peripheral blood monocytes to differentiate into immunogenic dendritic cells in vitro |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8115579/ https://www.ncbi.nlm.nih.gov/pubmed/33970783 http://dx.doi.org/10.1080/19490976.2021.1921927 |
work_keys_str_mv | AT radojevicdusan fecalmicrobiotacompositionassociateswiththecapacityofhumanperipheralbloodmonocytestodifferentiateintoimmunogenicdendriticcellsinvitro AT tomicsergej fecalmicrobiotacompositionassociateswiththecapacityofhumanperipheralbloodmonocytestodifferentiateintoimmunogenicdendriticcellsinvitro AT mihajlovicdusan fecalmicrobiotacompositionassociateswiththecapacityofhumanperipheralbloodmonocytestodifferentiateintoimmunogenicdendriticcellsinvitro AT tolinackimaja fecalmicrobiotacompositionassociateswiththecapacityofhumanperipheralbloodmonocytestodifferentiateintoimmunogenicdendriticcellsinvitro AT pavlovicbojan fecalmicrobiotacompositionassociateswiththecapacityofhumanperipheralbloodmonocytestodifferentiateintoimmunogenicdendriticcellsinvitro AT vucevicdragana fecalmicrobiotacompositionassociateswiththecapacityofhumanperipheralbloodmonocytestodifferentiateintoimmunogenicdendriticcellsinvitro AT bojicsvetlana fecalmicrobiotacompositionassociateswiththecapacityofhumanperipheralbloodmonocytestodifferentiateintoimmunogenicdendriticcellsinvitro AT golicnatasa fecalmicrobiotacompositionassociateswiththecapacityofhumanperipheralbloodmonocytestodifferentiateintoimmunogenicdendriticcellsinvitro AT colicmiodrag fecalmicrobiotacompositionassociateswiththecapacityofhumanperipheralbloodmonocytestodifferentiateintoimmunogenicdendriticcellsinvitro AT đokicjelena fecalmicrobiotacompositionassociateswiththecapacityofhumanperipheralbloodmonocytestodifferentiateintoimmunogenicdendriticcellsinvitro |