CbpF Mediates Inhibition of T Cell Function Through CEACAM1 Activation

Overview

Journal Front Cell Infect Microbiol

Specialties Cell Biology
Infectious Diseases
Microbiology

Date 2021 Aug 2

PMID 34336716

Citations 25

Authors

Johanna Galaski

Amjad Shhadeh

Ariana Umana

Christopher C Yoo

Ludovica Arpinati

Batya Isaacson

Orit Berhani

Bernhard B Singer

Daniel J Slade

Gilad Bachrach

Ofer Mandelboim

Affiliations

Soon will be listed here.

Abstract

is an anaerobic bacterium that is associated with several tumor entities and promotes tumorigenesis. Recent evidence suggests that binds the inhibitory receptor carcinoembryonic antigen cell adhesion molecule 1 (CEACAM1) 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 mutants lacking the type 5c trimeric autotransporter adhesins fvcA (CbpF), fvcB, fvcC, and fvcD, we show that 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 uses its surface protein CbpF to inhibit T cell function by activating CEACAM1.

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