Fusobacterium nucleatum CbpF Mediates Inhibition of T Cell Function Through CEACAM1 Activation

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dc.contributor.authorGalaski, Johannaen
dc.contributor.authorShhadeh, Amjaden
dc.contributor.authorUmana, Arianaen
dc.contributor.authorYoo, Christopher C.en
dc.contributor.authorArpinati, Ludovicaen
dc.contributor.authorIsaacson, Batyaen
dc.contributor.authorBerhani, Oriten
dc.contributor.authorSinger, Bernhard B.en
dc.contributor.authorSlade, Daniel J.en
dc.contributor.authorBachrach, Giladen
dc.contributor.authorMandelboim, Oferen
dc.date.accessioned2022-04-08T13:06:44Zen
dc.date.available2022-04-08T13:06:44Zen
dc.date.issued2021-07-15en
dc.description.abstractF. 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.en
dc.description.notesJG is supported by the German Research Foundation (DFG; project number 429842436) with a postdoctoral research fellowship. This work was supported by the Israel Science Foundation (Moked grant), the GIF Foundation, the ICRF professorship grant, the ISF Israel-China grant, the MOST-DKFZ grant, and by the ERC Marie Curie grant.en
dc.description.sponsorshipGerman Research Foundation (DFG)German Research Foundation (DFG) [429842436]; Israel Science Foundation (Moked grant); GIF FoundationGerman-Israeli Foundation for Scientific Research and Development; ICRF professorship grant; ISF Israel-China grant; MOST-DKFZ grant; ERC Marie Curie granten
dc.description.versionPublished versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.3389/fcimb.2021.692544en
dc.identifier.issn2235-2988en
dc.identifier.other692544en
dc.identifier.pmid34336716en
dc.identifier.urihttp://hdl.handle.net/10919/109610en
dc.identifier.volume11en
dc.language.isoenen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectF. nucleatumen
dc.subjectCbpFen
dc.subjecttrimeric autotransporter adhesinsen
dc.subjectCEACAM1en
dc.subjectCEAen
dc.titleFusobacterium nucleatum CbpF Mediates Inhibition of T Cell Function Through CEACAM1 Activationen
dc.title.serialFrontiers in Cellular and Infection Microbiologyen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten

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