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Siglec-7 Mediates Immunomodulation by Colorectal Cancer-Associated Fusobacterium nucleatum ssp. animalis

Fusobacterium nucleatum is involved in the development of colorectal cancer (CRC) through innate immune cell modulation. However, the receptors of the interaction between F. nucleatum ssp. and immune cells remain largely undetermined. Here, we showed that F. nucleatum ssp. animalis interacts with Si...

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Autores principales: Lamprinaki, Dimitra, Garcia-Vello, Pilar, Marchetti, Roberta, Hellmich, Charlotte, McCord, Kelli A., Bowles, Kristian M., Macauley, Matthew S., Silipo, Alba, De Castro, Cristina, Crocker, Paul R., Juge, Nathalie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8517482/
https://www.ncbi.nlm.nih.gov/pubmed/34659241
http://dx.doi.org/10.3389/fimmu.2021.744184
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author Lamprinaki, Dimitra
Garcia-Vello, Pilar
Marchetti, Roberta
Hellmich, Charlotte
McCord, Kelli A.
Bowles, Kristian M.
Macauley, Matthew S.
Silipo, Alba
De Castro, Cristina
Crocker, Paul R.
Juge, Nathalie
author_facet Lamprinaki, Dimitra
Garcia-Vello, Pilar
Marchetti, Roberta
Hellmich, Charlotte
McCord, Kelli A.
Bowles, Kristian M.
Macauley, Matthew S.
Silipo, Alba
De Castro, Cristina
Crocker, Paul R.
Juge, Nathalie
author_sort Lamprinaki, Dimitra
collection PubMed
description Fusobacterium nucleatum is involved in the development of colorectal cancer (CRC) through innate immune cell modulation. However, the receptors of the interaction between F. nucleatum ssp. and immune cells remain largely undetermined. Here, we showed that F. nucleatum ssp. animalis interacts with Siglecs (sialic acid–binding immunoglobulin-like lectins) expressed on innate immune cells with highest binding to Siglec-7. Binding to Siglec-7 was also observed using F. nucleatum-derived outer membrane vesicles (OMVs) and lipopolysaccharide (LPS). F. nucleatum and its derived OMVs or LPS induced a pro-inflammatory profile in human monocyte-derived dendritic cells (moDCs) and a tumour associated profile in human monocyte-derived macrophages (moMϕs). Siglec-7 silencing in moDCs or CRISPR-cas9 Siglec-7-depletion of U-937 macrophage cells altered F. nucleatum induced cytokine but not marker expression. The molecular interaction between Siglec-7 and the LPS O-antigen purified from F. nucleatum ssp. animalis was further characterised by saturation transfer difference (STD) NMR spectroscopy, revealing novel ligands for Siglec-7. Together, these data support a new role for Siglec-7 in mediating immune modulation by F. nucleatum strains and their OMVs through recognition of LPS on the bacterial cell surface. This opens a new dimension in our understanding of how F. nucleatum promotes CRC progression through the generation of a pro-inflammatory environment and provides a molecular lead for the development of novel cancer therapeutic approaches targeting F. nucleatum-Siglec-7 interaction.
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spelling pubmed-85174822021-10-16 Siglec-7 Mediates Immunomodulation by Colorectal Cancer-Associated Fusobacterium nucleatum ssp. animalis Lamprinaki, Dimitra Garcia-Vello, Pilar Marchetti, Roberta Hellmich, Charlotte McCord, Kelli A. Bowles, Kristian M. Macauley, Matthew S. Silipo, Alba De Castro, Cristina Crocker, Paul R. Juge, Nathalie Front Immunol Immunology Fusobacterium nucleatum is involved in the development of colorectal cancer (CRC) through innate immune cell modulation. However, the receptors of the interaction between F. nucleatum ssp. and immune cells remain largely undetermined. Here, we showed that F. nucleatum ssp. animalis interacts with Siglecs (sialic acid–binding immunoglobulin-like lectins) expressed on innate immune cells with highest binding to Siglec-7. Binding to Siglec-7 was also observed using F. nucleatum-derived outer membrane vesicles (OMVs) and lipopolysaccharide (LPS). F. nucleatum and its derived OMVs or LPS induced a pro-inflammatory profile in human monocyte-derived dendritic cells (moDCs) and a tumour associated profile in human monocyte-derived macrophages (moMϕs). Siglec-7 silencing in moDCs or CRISPR-cas9 Siglec-7-depletion of U-937 macrophage cells altered F. nucleatum induced cytokine but not marker expression. The molecular interaction between Siglec-7 and the LPS O-antigen purified from F. nucleatum ssp. animalis was further characterised by saturation transfer difference (STD) NMR spectroscopy, revealing novel ligands for Siglec-7. Together, these data support a new role for Siglec-7 in mediating immune modulation by F. nucleatum strains and their OMVs through recognition of LPS on the bacterial cell surface. This opens a new dimension in our understanding of how F. nucleatum promotes CRC progression through the generation of a pro-inflammatory environment and provides a molecular lead for the development of novel cancer therapeutic approaches targeting F. nucleatum-Siglec-7 interaction. Frontiers Media S.A. 2021-10-01 /pmc/articles/PMC8517482/ /pubmed/34659241 http://dx.doi.org/10.3389/fimmu.2021.744184 Text en Copyright © 2021 Lamprinaki, Garcia-Vello, Marchetti, Hellmich, McCord, Bowles, Macauley, Silipo, De Castro, Crocker and Juge 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
Lamprinaki, Dimitra
Garcia-Vello, Pilar
Marchetti, Roberta
Hellmich, Charlotte
McCord, Kelli A.
Bowles, Kristian M.
Macauley, Matthew S.
Silipo, Alba
De Castro, Cristina
Crocker, Paul R.
Juge, Nathalie
Siglec-7 Mediates Immunomodulation by Colorectal Cancer-Associated Fusobacterium nucleatum ssp. animalis
title Siglec-7 Mediates Immunomodulation by Colorectal Cancer-Associated Fusobacterium nucleatum ssp. animalis
title_full Siglec-7 Mediates Immunomodulation by Colorectal Cancer-Associated Fusobacterium nucleatum ssp. animalis
title_fullStr Siglec-7 Mediates Immunomodulation by Colorectal Cancer-Associated Fusobacterium nucleatum ssp. animalis
title_full_unstemmed Siglec-7 Mediates Immunomodulation by Colorectal Cancer-Associated Fusobacterium nucleatum ssp. animalis
title_short Siglec-7 Mediates Immunomodulation by Colorectal Cancer-Associated Fusobacterium nucleatum ssp. animalis
title_sort siglec-7 mediates immunomodulation by colorectal cancer-associated fusobacterium nucleatum ssp. animalis
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8517482/
https://www.ncbi.nlm.nih.gov/pubmed/34659241
http://dx.doi.org/10.3389/fimmu.2021.744184
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