title: CEACAM1 dynamics during neisseria gonorrhoeae suppression of CD4+ T lymphocyte activation.
abstract: Neisseria gonorrhoeae colony opacity-associated (Opa) proteins bind to human carcinoembryonic antigen cellular adhesion molecules (CEACAM) found on host cells including T lymphocytes. Opa binding to CEACAM1 suppresses the activation of CD4(+) T cells in response to a variety of stimuli. In this study, we use primary human CD4(+) T cells isolated from peripheral blood to define the molecular events occurring subsequent to Opa-CEACAM1 binding. We establish that, in contrast to other cell types, T cells do not engulf N. gonorrhoeae upon CEACAM1 binding. Instead, the bacteria recruit CEACAM1 from intracellular stores and maintain it on the T cell surface. Upon TCR ligation, the co-engaged CEACAM1 becomes phosphorylated on tyrosine residues within the ITIMs apparent in the cytoplasmic domain. This allows the recruitment and subsequent activation of the src homology domain 2-containing tyrosine phosphatases SHP-1 and SHP-2 at the site of bacterial attachment, which prevents the normal tyrosine phosphorylation of the CD3zeta-chain and ZAP-70 kinase in response to TCR engagement. Combined, this dynamic response allows the bacteria to effectively harness the coinhibitory function of CEACAM1 to suppress the adaptive immune response at its earliest step.
authors.affiliation: Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Hannah S W
authors.initials: HS
authors.lastname: Lee
authors.forename: Mario A
authors.initials: MA
authors.lastname: Ostrowski
authors.forename: Scott D
authors.initials: SD
authors.lastname: Gray-Owen
mesh_terms: D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism*; D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism; D017252:CD3 Complex / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000382:microbiology*; D015815:Cell Adhesion Molecules / Q000276:immunology / Q000378:metabolism*; D006069:Gonorrhea / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology*; D018613:Microscopy, Confocal; D018448:Models, Immunological; D009344:Neisseria gonorrhoeae / Q000276:immunology*; D010766:Phosphorylation; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11 / Q000378:metabolism; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6 / Q000378:metabolism; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D001425:Bacterial Outer Membrane Proteins; D017252:CD3 Complex; C121704:CD3 antigen, zeta chain; C069847:CD66 antigens; D015815:Cell Adhesion Molecules; C090348:Opa protein, Neisseria; D051746:ZAP-70 Protein-Tyrosine Kinase; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6