title: Neisserial outer membrane vesicles bind the coinhibitory receptor carcinoembryonic antigen-related cellular adhesion molecule 1 and suppress CD4+ T lymphocyte function.
abstract: Pathogenic Neisseria bacteria naturally liberate outer membrane "blebs," which are presumed to contribute to pathology, and the detergent-extracted outer membrane vesicles (OMVs) from Neisseria meningitidis are currently employed as meningococcal vaccines in humans. While the composition of these vesicles reflects the bacteria from which they are derived, the functions of many of their constituent proteins remain unexplored. The neisserial colony opacity-associated Opa proteins function as adhesins, the majority of which mediate bacterial attachment to human carcinoembryonic antigen-related cellular adhesion molecules (CEACAMs). Herein, we demonstrate that the Opa proteins within OMV preparations retain the capacity to bind the immunoreceptor tyrosine-based inhibitory motif-containing coinhibitory receptor CEACAM1. When CD4(+) T lymphocytes were exposed to OMVs from Opa-expressing bacteria, their activation and proliferation in response to a variety of stimuli were effectively halted. This potent immunosuppressive effect suggests that localized infection will generate a "zone of inhibition" resulting from the diffusion of membrane blebs into the surrounding tissues. Moreover, it demonstrates that OMV-based vaccines must be developed from strains that lack CEACAM1-binding Opa variants.
authors.affiliation: Department of Medical Genetics and Microbiology, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
authors.forename: Hannah S W
authors.initials: HS
authors.lastname: Lee
authors.forename: Ian C
authors.initials: IC
authors.lastname: Boulton
authors.forename: Karen
authors.initials: K
authors.lastname: Reddin
authors.forename: Henry
authors.initials: H
authors.lastname: Wong
authors.forename: Denise
authors.initials: D
authors.lastname: Halliwell
authors.forename: Ofer
authors.initials: O
authors.lastname: Mandelboim
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Gorringe
authors.forename: Scott D
authors.initials: SD
authors.lastname: Gray-Owen
mesh_terms: D020816:Amino Acid Motifs / Q000276:immunology; D015703:Antigens, CD / Q000378:metabolism* / Q000502:physiology; D001422:Bacterial Adhesion; D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism* / Q000502:physiology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism* / Q000502:physiology; D002473:Cell Wall / Q000502:physiology; D002478:Cells, Cultured; D006131:Growth Inhibitors / Q000378:metabolism / Q000502:physiology; D006801:Humans; D007165:Immunosuppression Therapy; D019169:Jurkat Cells; D042806:Neisseria lactamica / Q000276:immunology; D009345:Neisseria meningitidis / Q000276:immunology*; D011971:Receptors, Immunologic / Q000378:metabolism* / Q000502:physiology; D014443:Tyrosine / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D001425:Bacterial Outer Membrane Proteins; C069847:CD66 antigens; D015815:Cell Adhesion Molecules; D006131:Growth Inhibitors; D011971:Receptors, Immunologic; C090348:Opa protein, Neisseria; D014443:Tyrosine