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 

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

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=11

YEAR=2021

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2021.692544

DOI=10.3389/fcimb.2021.692544

ISSN=2235-2988

ABSTRACT=<p><italic>F. nucleatum</italic> is an anaerobic bacterium that is associated with several tumor entities and promotes tumorigenesis. Recent evidence suggests that <italic>F. nucleatum</italic> binds the inhibitory receptor carcinoembryonic antigen cell adhesion molecule 1 (CEACAM1) <italic>via</italic> 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 <italic>F. nucleatum</italic> mutants lacking the type 5c trimeric autotransporter adhesins fvcA (CbpF), fvcB, fvcC, and fvcD, we show that <italic>F. nucleatum</italic> 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<sup>+</sup> T cell response. Thus, we characterize an immune evasion mechanism in which <italic>F. nucleatum</italic> uses its surface protein CbpF to inhibit T cell function by activating CEACAM1.</p>