Neisserial Outer Membrane Vesicles Bind the Coinhibitory Receptor Carcinoembryonic Antigen-Related Cellular Adhesion Molecule 1 and Suppress CD4⁺ T Lymphocyte Function

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 o...

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Veröffentlicht in:Infection and Immunity 2007-09, Vol.75 (9), p.4449-4455
Hauptverfasser: Lee, Hannah S.W, Boulton, Ian C, Reddin, Karen, Wong, Henry, Halliwell, Denise, Mandelboim, Ofer, Gorringe, Andrew R, Gray-Owen, Scott D
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container_end_page 4455
container_issue 9
container_start_page 4449
container_title Infection and Immunity
container_volume 75
creator Lee, Hannah S.W
Boulton, Ian C
Reddin, Karen
Wong, Henry
Halliwell, Denise
Mandelboim, Ofer
Gorringe, Andrew R
Gray-Owen, Scott D
description 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.
doi_str_mv 10.1128/IAI.00222-07
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subjects Amino Acid Motifs - immunology
Antigens, CD - metabolism
Antigens, CD - physiology
Bacterial Adhesion
Bacterial Outer Membrane Proteins - metabolism
Bacterial Outer Membrane Proteins - physiology
Bacteriology
Biological and medical sciences
CD4-Positive T-Lymphocytes - cytology
CD4-Positive T-Lymphocytes - immunology
CD4-Positive T-Lymphocytes - metabolism
Cell Adhesion Molecules - metabolism
Cell Adhesion Molecules - physiology
Cell Wall - physiology
Cells, Cultured
Fundamental and applied biological sciences. Psychology
Growth Inhibitors - metabolism
Growth Inhibitors - physiology
Host Response and Inflammation
Humans
Immunosuppression
Jurkat Cells
Microbiology
Neisseria lactamica - immunology
Neisseria meningitidis - immunology
Pathogenicity, virulence, toxins, bacteriocins, pyrogens, host-bacteria relations, miscellaneous strains
Receptors, Immunologic - metabolism
Receptors, Immunologic - physiology
Tyrosine - metabolism
title Neisserial Outer Membrane Vesicles Bind the Coinhibitory Receptor Carcinoembryonic Antigen-Related Cellular Adhesion Molecule 1 and Suppress CD4⁺ T Lymphocyte Function
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