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Fusobacterium nucleatum CbpF Mediates Inhibition of T Cell Function Through CEACAM1 Activation
F. nucleatum is an anaerobic bacterium that is associated with several tumor entities and promotes tumorigenesis. Recent evidence suggests that F. nucleatum binds the inhibitory receptor carcinoembryonic antigen cell adhesion molecule 1 (CEACAM1) via the trimeric autotransporter adhesin CbpF. Howeve...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8319768/ https://www.ncbi.nlm.nih.gov/pubmed/34336716 http://dx.doi.org/10.3389/fcimb.2021.692544 |
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author | Galaski, Johanna Shhadeh, Amjad Umaña, Ariana Yoo, Christopher C. Arpinati, Ludovica Isaacson, Batya Berhani, Orit Singer, Bernhard B. Slade, Daniel J. Bachrach, Gilad Mandelboim, Ofer |
author_facet | Galaski, Johanna Shhadeh, Amjad Umaña, Ariana Yoo, Christopher C. Arpinati, Ludovica Isaacson, Batya Berhani, Orit Singer, Bernhard B. Slade, Daniel J. Bachrach, Gilad Mandelboim, Ofer |
author_sort | Galaski, Johanna |
collection | PubMed |
description | F. nucleatum is an anaerobic bacterium that is associated with several tumor entities and promotes tumorigenesis. Recent evidence suggests that F. nucleatum binds the inhibitory receptor carcinoembryonic antigen cell adhesion molecule 1 (CEACAM1) via the trimeric autotransporter adhesin CbpF. However, whether this binding is functional or whether other fusobacterial trimeric autotransporter adhesins are involved in CEACAM1 activation is unknown. In this study, using F. nucleatum mutants lacking the type 5c trimeric autotransporter adhesins fvcA (CbpF), fvcB, fvcC, and fvcD, we show that F. nucleatum CbpF binds and activates CEACAM1 and also binds carcinoembryonic antigen (CEA), a tumor-associated protein. We further find that CEACAM antibodies directed against the CEACAM N-terminal domain block the CbpF-CEACAM1 interaction. In functional assays, we demonstrate CbpF-dependent inhibition of CD4(+) T cell response. Thus, we characterize an immune evasion mechanism in which F. nucleatum uses its surface protein CbpF to inhibit T cell function by activating CEACAM1. |
format | Online Article Text |
id | pubmed-8319768 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-83197682021-07-30 Fusobacterium nucleatum CbpF Mediates Inhibition of T Cell Function Through CEACAM1 Activation Galaski, Johanna Shhadeh, Amjad Umaña, Ariana Yoo, Christopher C. Arpinati, Ludovica Isaacson, Batya Berhani, Orit Singer, Bernhard B. Slade, Daniel J. Bachrach, Gilad Mandelboim, Ofer Front Cell Infect Microbiol Cellular and Infection Microbiology F. nucleatum is an anaerobic bacterium that is associated with several tumor entities and promotes tumorigenesis. Recent evidence suggests that F. nucleatum binds the inhibitory receptor carcinoembryonic antigen cell adhesion molecule 1 (CEACAM1) via the trimeric autotransporter adhesin CbpF. However, whether this binding is functional or whether other fusobacterial trimeric autotransporter adhesins are involved in CEACAM1 activation is unknown. In this study, using F. nucleatum mutants lacking the type 5c trimeric autotransporter adhesins fvcA (CbpF), fvcB, fvcC, and fvcD, we show that F. nucleatum CbpF binds and activates CEACAM1 and also binds carcinoembryonic antigen (CEA), a tumor-associated protein. We further find that CEACAM antibodies directed against the CEACAM N-terminal domain block the CbpF-CEACAM1 interaction. In functional assays, we demonstrate CbpF-dependent inhibition of CD4(+) T cell response. Thus, we characterize an immune evasion mechanism in which F. nucleatum uses its surface protein CbpF to inhibit T cell function by activating CEACAM1. Frontiers Media S.A. 2021-07-15 /pmc/articles/PMC8319768/ /pubmed/34336716 http://dx.doi.org/10.3389/fcimb.2021.692544 Text en Copyright © 2021 Galaski, Shhadeh, Umaña, Yoo, Arpinati, Isaacson, Berhani, Singer, Slade, Bachrach and Mandelboim 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 | Cellular and Infection Microbiology Galaski, Johanna Shhadeh, Amjad Umaña, Ariana Yoo, Christopher C. Arpinati, Ludovica Isaacson, Batya Berhani, Orit Singer, Bernhard B. Slade, Daniel J. Bachrach, Gilad Mandelboim, Ofer Fusobacterium nucleatum CbpF Mediates Inhibition of T Cell Function Through CEACAM1 Activation |
title |
Fusobacterium nucleatum CbpF Mediates Inhibition of T Cell Function Through CEACAM1 Activation |
title_full |
Fusobacterium nucleatum CbpF Mediates Inhibition of T Cell Function Through CEACAM1 Activation |
title_fullStr |
Fusobacterium nucleatum CbpF Mediates Inhibition of T Cell Function Through CEACAM1 Activation |
title_full_unstemmed |
Fusobacterium nucleatum CbpF Mediates Inhibition of T Cell Function Through CEACAM1 Activation |
title_short |
Fusobacterium nucleatum CbpF Mediates Inhibition of T Cell Function Through CEACAM1 Activation |
title_sort | fusobacterium nucleatum cbpf mediates inhibition of t cell function through ceacam1 activation |
topic | Cellular and Infection Microbiology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8319768/ https://www.ncbi.nlm.nih.gov/pubmed/34336716 http://dx.doi.org/10.3389/fcimb.2021.692544 |
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