Shotgun metagenomics reveals gut microbiota features associated with the efficacy of myeloid derived suppressor cells in the prevention of neuroinflammation
Authors
Bekić, MarinaĐokić, Jelena
Radojević, Dušan
Vučević, Dragana
Vasilev, Saša
Tomić, Sergej
Contributors
Morić, IvanaĐorđević, Valentina
Conference object (Published version)
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© 2023 Institute of Molecular Genetics and Genetic Engineering, University of Belgrade
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Show full item recordAbstract
Although genetic predisposition to Multiple Sclerosis (MS) may play an essential role in disease
development, myeloid cell overactivation and gut microbiota dysbiosis are key contributors to MS
pathogenesis. Myeloid-Derived Suppressor Cells (MDSC)s are immature myeloid cells with strong
immunosuppressive functions which can be exploited in the treatment of autoimmune diseases.
Considering the limited data on MDSCs application in MS therapy and their poorly studied effects
on the gut microbiota, we have investigated the therapeutic potential of mice MDSC differentiated
according to the standard protocol (MDSC) and modified with the addition of prostaglandin (PG)
E2 (MDSC-PGE2) to ameliorate experimental autoimmune encephalomyelitis (EAE) induced with
MOG35-55/CFA/PtX in C57BL/6 mice. Additionally, we analyzed the changes in gut microbiota
features in control and MDSC-treated animals by using a shotgun metagenomics approach. In
mice, PGE2-activated MDSC significantly inhibited ...the onset and clinical course of EAE. This effect
correlated with increased IL-10, TGF-β, IL-4 production, and Arginase-1 level in MDSC-PGE2,
as well as with reduced leukocyte infiltrates in the spinal cord. MDSC-PGE2 protective effect is
also reflected in the maintenance of gut microbiota composition based on Kraken2/Bracken2
and LEfSe analysis. We observed an increase of MS-associated species Romboutsia ilealis in
the control EAE group, while in both MDSC treatments the increase in relative abundances of
Muribaculum gordoncarteri and Duncaniella dubiosis, associated with immunoregulatory properties,
was observed. Microbial metabolic pathways profiling using Humann3 pipeline also reveals the
increase in pathways involved in the production of potentially immunoregulatory metabolites
in the MDSC-PGE2 group. In conclusion, we pointed to the significant association between the
efficacy of MDSC-PGE2 treatment and gut microbiota features which can be further exploited in
order to improve MDSC-based EAE therapy.
Keywords:
myeloid derived suppressor cells / gut microbiota / functional pathways / multiple sclerosis / immunoregulatory mechanismsSource:
4th Belgrade Bioinformatics Conference, 2023, 4, 97-97Publisher:
- Belgrade : Institute of molecular genetics and genetic engineering
Funding / projects:
- Ministry of Science, Technological Development and Innovation of the Republic of Serbia, institutional funding - 200042 (University of Belgrade, Institute of Molecular Genetics and Genetic Engineering) (RS-MESTD-inst-2020-200042)
- Ministry of Science, Technological Development and Innovation of the Republic of Serbia, institutional funding - 200019 (University of Belgrade, Institute for the Application of Nuclear Energy - INEP) (RS-MESTD-inst-2020-200019)
- Nano-MDSC-Thera - Novel Immunotherapeutic Approaches for Autoimmune Diseases Based on Myeloid Derived Suppressor Cells Induced By Nanomaterials (RS-ScienceFundRS-Promis-6062673)
Note:
- Book of abstract: 4th Belgrade Bioinformatics Conference, June 19-23, 2023
Institution/Community
Institut za molekularnu genetiku i genetičko inženjerstvoTY - CONF AU - Bekić, Marina AU - Đokić, Jelena AU - Radojević, Dušan AU - Vučević, Dragana AU - Vasilev, Saša AU - Tomić, Sergej PY - 2023 UR - https://belbi.bg.ac.rs/ UR - https://imagine.imgge.bg.ac.rs/handle/123456789/2042 AB - Although genetic predisposition to Multiple Sclerosis (MS) may play an essential role in disease development, myeloid cell overactivation and gut microbiota dysbiosis are key contributors to MS pathogenesis. Myeloid-Derived Suppressor Cells (MDSC)s are immature myeloid cells with strong immunosuppressive functions which can be exploited in the treatment of autoimmune diseases. Considering the limited data on MDSCs application in MS therapy and their poorly studied effects on the gut microbiota, we have investigated the therapeutic potential of mice MDSC differentiated according to the standard protocol (MDSC) and modified with the addition of prostaglandin (PG) E2 (MDSC-PGE2) to ameliorate experimental autoimmune encephalomyelitis (EAE) induced with MOG35-55/CFA/PtX in C57BL/6 mice. Additionally, we analyzed the changes in gut microbiota features in control and MDSC-treated animals by using a shotgun metagenomics approach. In mice, PGE2-activated MDSC significantly inhibited the onset and clinical course of EAE. This effect correlated with increased IL-10, TGF-β, IL-4 production, and Arginase-1 level in MDSC-PGE2, as well as with reduced leukocyte infiltrates in the spinal cord. MDSC-PGE2 protective effect is also reflected in the maintenance of gut microbiota composition based on Kraken2/Bracken2 and LEfSe analysis. We observed an increase of MS-associated species Romboutsia ilealis in the control EAE group, while in both MDSC treatments the increase in relative abundances of Muribaculum gordoncarteri and Duncaniella dubiosis, associated with immunoregulatory properties, was observed. Microbial metabolic pathways profiling using Humann3 pipeline also reveals the increase in pathways involved in the production of potentially immunoregulatory metabolites in the MDSC-PGE2 group. In conclusion, we pointed to the significant association between the efficacy of MDSC-PGE2 treatment and gut microbiota features which can be further exploited in order to improve MDSC-based EAE therapy. PB - Belgrade : Institute of molecular genetics and genetic engineering C3 - 4th Belgrade Bioinformatics Conference T1 - Shotgun metagenomics reveals gut microbiota features associated with the efficacy of myeloid derived suppressor cells in the prevention of neuroinflammation EP - 97 SP - 97 VL - 4 UR - https://hdl.handle.net/21.15107/rcub_imagine_2042 ER -
@conference{ author = "Bekić, Marina and Đokić, Jelena and Radojević, Dušan and Vučević, Dragana and Vasilev, Saša and Tomić, Sergej", year = "2023", abstract = "Although genetic predisposition to Multiple Sclerosis (MS) may play an essential role in disease development, myeloid cell overactivation and gut microbiota dysbiosis are key contributors to MS pathogenesis. Myeloid-Derived Suppressor Cells (MDSC)s are immature myeloid cells with strong immunosuppressive functions which can be exploited in the treatment of autoimmune diseases. Considering the limited data on MDSCs application in MS therapy and their poorly studied effects on the gut microbiota, we have investigated the therapeutic potential of mice MDSC differentiated according to the standard protocol (MDSC) and modified with the addition of prostaglandin (PG) E2 (MDSC-PGE2) to ameliorate experimental autoimmune encephalomyelitis (EAE) induced with MOG35-55/CFA/PtX in C57BL/6 mice. Additionally, we analyzed the changes in gut microbiota features in control and MDSC-treated animals by using a shotgun metagenomics approach. In mice, PGE2-activated MDSC significantly inhibited the onset and clinical course of EAE. This effect correlated with increased IL-10, TGF-β, IL-4 production, and Arginase-1 level in MDSC-PGE2, as well as with reduced leukocyte infiltrates in the spinal cord. MDSC-PGE2 protective effect is also reflected in the maintenance of gut microbiota composition based on Kraken2/Bracken2 and LEfSe analysis. We observed an increase of MS-associated species Romboutsia ilealis in the control EAE group, while in both MDSC treatments the increase in relative abundances of Muribaculum gordoncarteri and Duncaniella dubiosis, associated with immunoregulatory properties, was observed. Microbial metabolic pathways profiling using Humann3 pipeline also reveals the increase in pathways involved in the production of potentially immunoregulatory metabolites in the MDSC-PGE2 group. In conclusion, we pointed to the significant association between the efficacy of MDSC-PGE2 treatment and gut microbiota features which can be further exploited in order to improve MDSC-based EAE therapy.", publisher = "Belgrade : Institute of molecular genetics and genetic engineering", journal = "4th Belgrade Bioinformatics Conference", title = "Shotgun metagenomics reveals gut microbiota features associated with the efficacy of myeloid derived suppressor cells in the prevention of neuroinflammation", pages = "97-97", volume = "4", url = "https://hdl.handle.net/21.15107/rcub_imagine_2042" }
Bekić, M., Đokić, J., Radojević, D., Vučević, D., Vasilev, S.,& Tomić, S.. (2023). Shotgun metagenomics reveals gut microbiota features associated with the efficacy of myeloid derived suppressor cells in the prevention of neuroinflammation. in 4th Belgrade Bioinformatics Conference Belgrade : Institute of molecular genetics and genetic engineering., 4, 97-97. https://hdl.handle.net/21.15107/rcub_imagine_2042
Bekić M, Đokić J, Radojević D, Vučević D, Vasilev S, Tomić S. Shotgun metagenomics reveals gut microbiota features associated with the efficacy of myeloid derived suppressor cells in the prevention of neuroinflammation. in 4th Belgrade Bioinformatics Conference. 2023;4:97-97. https://hdl.handle.net/21.15107/rcub_imagine_2042 .
Bekić, Marina, Đokić, Jelena, Radojević, Dušan, Vučević, Dragana, Vasilev, Saša, Tomić, Sergej, "Shotgun metagenomics reveals gut microbiota features associated with the efficacy of myeloid derived suppressor cells in the prevention of neuroinflammation" in 4th Belgrade Bioinformatics Conference, 4 (2023):97-97, https://hdl.handle.net/21.15107/rcub_imagine_2042 .