Fecal microbiota composition associates with the capacity of human peripheral blood monocytes to differentiate into immunogenic dendritic cells in vitro
Аутори
Radojević, DušanTomić, Sergej
Mihajlović, Dusan
Tolinački, Maja
Pavlović, Bojan
Vucević, Dragana
Bojić, Svetlana
Golić, Nataša
Čolić, Miodrag
Đokić, Jelena
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
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 alpha-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-alpha, I...L-6, IL-8) and IL-12p70/IL-10 ratio, all of which correlated with their lower maturation potential and immunogenicity upon stimulation with LPS/IFN gamma, a well-known Th1 polarizing cocktail. In contrast, imDCs generated from donors with lower alpha-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-alpha, 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.
Кључне речи:
SCFA / myeloid cell therapy / monocyte derived dendritic cells / Gut microbiota / anti-cancer vaccineИзвор:
Gut Microbes, 2021, 13, 1Издавач:
- Taylor & Francis Inc, Philadelphia
Финансирање / пројекти:
- Nano-MDSC-Thera - Novel Immunotherapeutic Approaches for Autoimmune Diseases Based on Myeloid Derived Suppressor Cells Induced By Nanomaterials (RS-ScienceFundRS-Promis-6062673)
- Министарство науке, технолошког развоја и иновација Републике Србије, институционално финансирање - 200019 (Универзитет у Београду, Институт за примену нуклеарне енергије - ИНЕП) (RS-MESTD-inst-2020-200019)
- Министарство науке, технолошког развоја и иновација Републике Србије, институционално финансирање - 200042 (Универзитет у Београду, Институт за молекуларну генетику и генетичко инжењерство) (RS-MESTD-inst-2020-200042)
DOI: 10.1080/19490976.2021.1921927
ISSN: 1949-0976
PubMed: 33970783
WoS: 000709853200001
Scopus: 2-s2.0-85105767003
Институција/група
Institut za molekularnu genetiku i genetičko inženjerstvoTY - JOUR AU - Radojević, Dušan AU - Tomić, Sergej AU - Mihajlović, Dusan AU - Tolinački, Maja AU - Pavlović, Bojan AU - Vucević, Dragana AU - Bojić, Svetlana AU - Golić, Nataša AU - Čolić, Miodrag AU - Đokić, Jelena PY - 2021 UR - https://imagine.imgge.bg.ac.rs/handle/123456789/1475 AB - 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 alpha-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-alpha, 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/IFN gamma, a well-known Th1 polarizing cocktail. In contrast, imDCs generated from donors with lower alpha-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-alpha, 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. PB - Taylor & Francis Inc, Philadelphia T2 - Gut Microbes T1 - Fecal microbiota composition associates with the capacity of human peripheral blood monocytes to differentiate into immunogenic dendritic cells in vitro IS - 1 VL - 13 DO - 10.1080/19490976.2021.1921927 ER -
@article{ author = "Radojević, Dušan and Tomić, Sergej and Mihajlović, Dusan and Tolinački, Maja and Pavlović, Bojan and Vucević, Dragana and Bojić, Svetlana and Golić, Nataša and Čolić, Miodrag and Đokić, Jelena", year = "2021", abstract = "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 alpha-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-alpha, 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/IFN gamma, a well-known Th1 polarizing cocktail. In contrast, imDCs generated from donors with lower alpha-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-alpha, 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.", publisher = "Taylor & Francis Inc, Philadelphia", journal = "Gut Microbes", title = "Fecal microbiota composition associates with the capacity of human peripheral blood monocytes to differentiate into immunogenic dendritic cells in vitro", number = "1", volume = "13", doi = "10.1080/19490976.2021.1921927" }
Radojević, D., Tomić, S., Mihajlović, D., Tolinački, M., Pavlović, B., Vucević, D., Bojić, S., Golić, N., Čolić, M.,& Đokić, J.. (2021). Fecal microbiota composition associates with the capacity of human peripheral blood monocytes to differentiate into immunogenic dendritic cells in vitro. in Gut Microbes Taylor & Francis Inc, Philadelphia., 13(1). https://doi.org/10.1080/19490976.2021.1921927
Radojević D, Tomić S, Mihajlović D, Tolinački M, Pavlović B, Vucević D, Bojić S, Golić N, Čolić M, Đokić J. Fecal microbiota composition associates with the capacity of human peripheral blood monocytes to differentiate into immunogenic dendritic cells in vitro. in Gut Microbes. 2021;13(1). doi:10.1080/19490976.2021.1921927 .
Radojević, Dušan, Tomić, Sergej, Mihajlović, Dusan, Tolinački, Maja, Pavlović, Bojan, Vucević, 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" in Gut Microbes, 13, no. 1 (2021), https://doi.org/10.1080/19490976.2021.1921927 . .